Progress in Stem Cell (PSC) (ISSN 2199-4633) is the best Open Access journal that acts as a forum for translational research into stem cell therapies. PSC is scientific journal that overlays the study of Cancer stem cells, Stem cell therapy, Stem-cell transplantation, human embryonic stem cells, Neural stem cells, Murine Embryonic Stem Cells, Adult stem cell, Pancreatic stem cells, etc. PSC is a peer-reviewed journal that focuses on the areas of established and emerging concepts in stem cell research and their assorted disease therapies. It provides an opportunity to share the scientific information among the clinical & medical scientists and researchers.
Copyright The Author(s) 2017. This article is published with open access by BioMedPress. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Impact of body mass index on stromal vascular fraction cell yield from human lipoaspirates
Background: The stromal vascular fraction (SVF) of adipose tissue is a critical source of regenerative cells for autologous therapies. While donor-related factors like age have been studied, the influence of Body Mass Index (BMI) on SVF yield remains unclear. This study aimed to determine if a correlation exists between patient BMI and the number of nucleated cells isolated from lipoaspirates. Methods: Adipose tissue was collected from 48 female donors undergoing elective liposuction. Samples were processed using a standardized, point-of-care system (GID platform) for SVF isolation. The total nucleated cell count per milliliter of processed adipose tissue was determined and correlated with the donor's BMI. Results: The mean SVF yield was cells/mL. A significant positive correlation (Pearson r = 0.52, P < 0.001) was observed between increasing BMI and SVF cell yield. Donors with a BMI ≥ 25 kg/m² yielded significantly more cells than those with a BMI < 22 kg/m². Conclusions: Using a consistent harvesting site and processing technique, we conclude that higher BMI in female patients is associated with a greater yield of SVF cells from abdominal adipose tissue. This suggests that adipose tissue cellularity or composition varies with body mass, which has implications for pre-surgical planning in cell-based therapies.
Copyright (c) 2025 Noor Haider, Mohammad James http://creativecommons.org/licenses/by/4.0
Mesenchymal stem cell therapy for chronic obstructive pulmonary disease: Mechanisms, clinical evidence, and therapeutic perspectives
Chronic Obstructive Pulmonary Disease (COPD) represents a significant global health burden characterized by progressive airflow limitation and persistent respiratory symptoms. Despite current pharmacological interventions, disease modification remains elusive. Mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative approach targeting the core inflammatory and destructive processes underlying COPD pathogenesis. This comprehensive review examines the mechanistic basis of MSC therapy, synthesizes clinical evidence from 25 registered trials and 9 published studies, and provides evidence-based recommendations for clinical translation. MSCs exert multifaceted therapeutic effects primarily through paracrine-mediated immunomodulation, anti-fibrotic activity, and tissue repair promotion. Clinical data demonstrate consistent safety profiles and significant improvements in symptom burden and exacerbation frequency, though without substantial changes in FEV1. Optimal protocols suggest intravenous administration of 100 million umbilical cord-derived MSCs in two doses over three months. While Phase III trials are warranted, MSC therapy offers a paradigm shift toward disease modification in COPD management.
Copyright (c) 2025 Phuong Thi-Bich Le, Phuc Van Pham http://creativecommons.org/licenses/by/4.0
The Effect of the Dental Stem Cell Secretome on Tissue Regeneration: A Systematic Review
Secretome therapy is a promising approach in tissue regeneration because it can reproduce most of the advantages of cell-based therapies. This review aims to investigate the most prominent effect of using dental-derived secretome on tissue regeneration using a systematic review approach. A systematic electronic search was conducted via the PubMed, Scopus and Wiley online library databases for studies published in English up to October 2020. All the articles from the databases were screened, and the criteria for inclusion and exclusion were applied. Forty papers were included in the study, whereby there were 16 in vitro studies and 11 in vivo studies with different animal models. No clinical trial has been reported yet. The most studied DSCs were human SHEDs (12 studies), followed by human DPSCs (11) and human PDLSCs (5). The majority of the studies used secretome from human SHEDs and DPSCs. TGF-ß 1 is the most frequently detected protein in the secretome, which comes from six types of DSCs, followed by NGF and NT-3, which were found in five different types of DSC secretome. The compositions of the secretome were found to promote the regeneration of the tissues through their neurogenic, angiogenic, osteogenic and odontogenic effects, with the majority of studies reviewed reporting using them for nondental tissue regeneration. From this review, DSC-CM reported favorable tissue regeneration potential; however, many factors need to be explored in future research with regard to the application of secretome delivery, particularly DSC-CM, in the clinical setting.
Copyright (c) 2022 Nusaibah Sakinah Nordin, Maryati Md Dasor, Farha Ariffin, Zurairah Berahim, Muhammad Huzaimi Haron
L-ascorbic acid-2-phosphate and Fibrin Substrate Enhances the Chondrogenic Differentiation of Human Adipose-derived Stem Cells
Background: Adipose-derived stem cells (ASCs) have been developed as a substitute for chondrocytes in cartilage tissue engineering. This study aimed to evaluate the potency of ascorbic acid to induce the chondrogenic differentiation of human ASCs cultured on fibrin substrate. Methods: Human ASCs were isolated by an enzymatic process and characterized. The fibrin scaffold was fabricated from human blood as a natural scaffold. The ASCs were cultured in 10% fetal bovine serum (FBS) supplemented by ascorbic acid in various concentrations (1, 3, 6 mg/ml) and a control without an ascorbic acid supplementation. The chondrogenic differentiation of the ASCs was evaluated involving glycosaminoglycan analysis, and the mRNA expression of type 2 collagen, aggrecan and type 1 collagen. Results: Chondrogenic differentiation occurred when the ASCs were supplemented by 3 mg/ml of ascorbic acid and cultured on a fibrin scaffold confirmed by glycosaminoglycan (GAG) analysis, and the mRNA expression of type 2 collagen and aggrecan. The expression of type 1 collagen, which is an osteogenic marker, was low. Conclusions: ASCs with a supplementation of 3mg/ml of ascorbic acid cultured on a fibrin substrate promotes chondrogenic differentiation.
Copyright (c) 2022 Imam Rosadi, Karina Karina, Viol Dhea Kharisma, Arif Nur Muhammad Ansori
Present Status of Research on the Regenerative Potential of Dental Pulp Stem Cells in Malaysia: A Systematic Review
Stem cells from human exfoliated deciduous teeth (SHED) or dental pulp stem cells (DPSCs) from permanent teeth are considered promising sources of mesenchymal stem cells. It requires a less invasive technique to isolate stem cells from exfoliated or permanent teeth. Hence this study aimed to identify the present status of research on the regenerative potential of SHED/DPSCs in Malaysia. The results indicate that only 60 articles were published in regenerative medicine from Malaysia till 5th July 2019. Only 16 tertiary institutes and four industries/clinics were involved in these studies. A poor pattern of collaboration has also been identified. Outcomes of this study have emphasized the conduction of more research on the regenerative potential of SHED/DPSCs, and active collaboration among the tertiary institutes and industries for successful translation of these cells from bench side to bedside.
Good manufacturing practice-compliant isolation and culture of human bone marrow mesenchymal stem cells
Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into some kinds of mesenchymal cells such as osteoblasts, chondroblasts and adipocytes. These cells were discovered for a long time and considered as the first discovered source of MSCs. BM-MSC transplantation was used to treat some diseases such as bone disease, myocardial infarction, stroke, diabetes mellitus… This study aimed to provide a new method to in vitro primarily culture and secondary culture of BM-MSCs that were compliant with good manufacturing practice for clinical applications. Bone marrow was aspirated from the hip bone using special needles and syringes. Mononuclear cells (MNCs) were isolated from bone marrow by BM-MSC extraction kit. These MNCs were cultured in the commercial medium – MSC-Cult supplemented with 10% activated platelet rich plasma (aPRP) to obtain BM-MSCs. The results showed that 100% samples of bone marrow can be successfully cultured to produce BM-MSCs. Obtained cells exhibited the MSC phenotypes, and maintained the stable and normal karyotype up to 10th passages, and failed to cause tumor in the mouse models. This research provided an advanced protocol for clinical applications of BM-MSCs.
Copyright (c) 2014 Phuc Van Pham, Nhan Lu-Chinh Phan, Dung Minh Le, Phuong Thi-Bich Le, Tung Dang-Xuan Tran, Ngoc Kim Phan
What are markers for breast cancer stem cells ?
Breast cancer stem cells were firstly discovered by Al-Hajj et al. (2003). Many scientists interested in targeting them as an important solution to "remove" the root of breast cancer. However, more and more publications showed that breast cancer stem cells are the heterogenous population that expression of some markers can be different between them. Particularly, some different markers were considered as markers of breast cancer stem cells. Therefore, what are gold standards of these cells? In this publication, we discussed some conflicts about markers of breast cancer stem cells and suggested some gold standards for breast cancer stem cells.
Copyright (c) 2016 Phuc Van Pham, Nhan Lu-Chinh Phan
Mesenchymal Stem Cells: vector for targeted cancer therapy
Mesenchymal stem cells (MSCs) have been studied extensively due to their potential to differentiate to cell types of varying lineages.Adipose tissue and umbilical cord blood are two tissues frequently used to obtain MSCs. Due to tumor tropism of MSCs and their ability to protect encoded cytotoxic genes, MSCs have garnered interest as a potential vector for targeted therapy, with limited damage to normal tissues. The tumor microenvironment plays a critical role in ensuring the survival of cancer cells through promotion of MSCs to differentiate into cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis. Through specific interactions between ligands and receptors expressed on MSCs and cancer cells, respectively,MSCs can home to necrotic tissues or inflamed sites in the body, including the tumor microenvironment. In fact, an inflammatory tumor environment is similar to a wound healing environment. This review discusses the preeminent characteristics of MSCs and their influence ontumor cell growth and metastasis. MSCs may represent an encouraging platform for cancer treatment. The combination of MSC and gene therapy represents a potentially outstanding strategy to specifically target and effectively destroy tumor.
Copyright (c) 2016 Binh Thanh Vu, Ngoc Kim Phan, Phuc Van Pham
In vitro expansion of mesenchymal stem cells for clinical use
Mesenchymal stem cells (MSCs) now are popular stem cells for clinical applications. To date, MSCs were accepted in various disease treatments with several FDA approved treatments in some countries. One important requirement for the clinical usage of stem cells is the production of stem cells. Actually, the treatment efficacy of MSC transplantation depends on the quality of transplanted MSCs. This review aimed to present some guidelines for MSC production according to good manufacturing practice that helps to maintain the quality of stem cells from batch to batch as well as the clinical satisfaction.
Copyright (c) 2016 Phuc Van Pham, Ngoc Bich Vu
STEM CELL AND CANCER STEM CELL: A Tale of Two Cells
Stem cells are vital for regenerating and repairing the organs such as the heart, lungs, skin, germ cells and other tissues. But the characteristics of normal stem cells and the discovery of origin of leukemia have headed the scientist to the hypothesis that cancer may initiate from stem cell-like cells. Cancer stem cells are now thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. There are some similarities and differences between CSCs and healthy stem cells in signaling pathways (Wnt/ β–catenin, Hh, Notch), epigenetic modifications, telomere maintenance, and degree of dependence on the stem cell niche, maintenance of multipotency and self-renewability of respective progenitor cells. Distinct and specific surface biomarker phenotypes can be used to distinguish CSC from other tumor cells and normal stem cells through single and combination of markers such as CD44, CD34+CD38− and CD133. Recently, miRNAs have been tried as a marker and therapeutic agents against cancers stem cell such as miR-34a, miR-199a, miR-181, miR-125b-2 and miR-128. However, targeting CSCs without harming their normal counterparts is an advantageous way in the design of novel therapies but many questions remain unknown.
Copyright (c) 2016 MdShaifur Rahman, Hossen Mohammad Jamil, Naznin Akhtar, K.M.T. Rahman, Rashedul Islam, S.M. Asaduzzaman
Culture Methods and Choice of Cells Makes a Difference in Outcome of Tissue Engineering- a Perspective
This perspective reviews the effects of different tissue engineering techniques, for induced differentiation of human embryonic stem cells into pulmonary lineage specific cells, and validating cell based regenerative therapy to ameliorate pulmonary degeneration. The etiology of degeneration differs from disease to disease. Likewise, strategies to regenerate lost tissues in its heterogeneity, should also cater to the regeneration process. To customize the same, researchers ought to device strategies to repair, replace or regenerate, in the spatio- temporal format, healthy tissues in their heterogeneous multi-functional existence, such that when transplanted in vitro, they may find their niche and integrate seamlessly into the tissue system and manifest full-fledged functional competence in order to reverse the erstwhile effects of degeneration. Cell based lung repair or regeneration is unquestionably the most promising agenda of regenerative medicine. In one of our studies, human embryonic stem cell (hESC) line H7 was successfully differentiated into three non-ciliated alveolar epithelial cells. In another study, BJNhem19 and BJNhem20 stem cell lines were used to induce similar guided endodermal differentiation into pulmonary lineage cells. Both studies were done using similar protocols, where the hESCs were first plated on gamma irradiated mouse embryonic fibroblast (MEF) feeder cells and undifferentiated hESCs were taken through embroid body formation. They were then subjected to induction into lung specific cells, by defined growth factors in Small Airways Growth Medium (SAGM) and Bronchiolar Endothelial Growth Media (BEGM). The H7 cells were found to express, both intracellularly and on their surfaces, characteristic marker proteins. However, the BJNhem19 and BJNhem20 cells showed poor differential potential, and could not be successfully differentiated into lung- specific cells. This difference in differentiation potential may be due to several intrinsic limitations, like genetic heterogeneity, anomalous morphogen receptivity or dormant/ unresponsive cytoplasmic determinants. These observations indicate that the choice of cells may play an important factor in tissue engineering. This review addresses the different culture methods and conditions needed for guided differentiation of stem cells. This perspective also discusses culture conditions of mesenchymal stem cells from different origins and dendritic stem cells from bone marrow.
Copyright (c) 2016 Srabani Kar, Shinjini Mitra, Ena Ray Banerjee
The progress of Stem cells in the treatment of diabetes mellitus type 1
Diabetes mellitus is a major health problem in the world. The total number of diabetic’s population is increasing every year. Currently used treatment of diabetes mellitus type 1 by controlling the blood sugar levels, doesn’t prevent complications which associate diabetes. The stem cell based therapy for diabetes aims to replace the diseased or lost cells of the pancreas with new cells using pluripotent or multipotent stem cells. Scientists successfully produced insulin secreting cell from different types of stem cells. In this article we briefly reviewed the progress made in the stem cell research for diabetes treatment.
Copyright (c) 2017 Nihad Elsadig Babiker, Alsadig Gassoum, Nahla E. Abdelraheem, Mohamed Abdelrahman Arbab, Sawsan Ahmed Hamed ALDeaf, Mohamad Ahmed Ali El-Sheikh, Hassan Hussein Musa
Co-injection of ETV-2 and HGF viral vectors significantly improve angiogenesis in mice with hindlimb ischemia
Introduction: Both ETV-2 and HGF factors are known to be important factors which trigger neo-angiogenesis both in vitro and in vivo models. This study aimed to treat hindlimb ischemia in mice by co-injection of ETV-2 and HGF viral vectors. Methods: ETV-2 and HGF vectors were prepared per previous publications. The mouse ischemic hindlimb model was performed by ligating and burning the artery at the hindlimb. ETV-2 and HGF viral vectors were co-injected into the ligated and burnt sites. Results: The results showed that co-injection of the vectors significantly improved angiogenesis as well as reduced leg loss in mice compared to placebo treatment. The percentage of mice who succumbed to ischemia was also significantly reduced compared to control. Conclusion: Overall, this study suggests a potential impact of combining ETV-2 and HGF to treat angiogenesis. Use of ETV-2 and HGF viral vectors can be a promising therapy for ischemia treatment in the future.
Copyright (c) 2017 Phuc Van Pham, Ngoc Bich Vu, Thuy Thi-Thanh Dao, Ha Thi-Ngan Le, Lan Thi Phi, Ngoc Kim Phan
Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection
Introduction: To date, there have been many studies indicating the positive effects of stem cells on treating liver cirrhosis. In this study, we used umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) for treatment in a mouse model of liver cirrhosis. Specifically, we determined and compared the effectiveness of two methods of MSC injection (tail vein versus portal vein). Methods: Liver cirrhosis in male Swiss mice (of age approximately 11 weeks or under) was induced by administration of carbon tetrachloride (CCl4; 1 ml/kg). One million UCB-MSCs were then transplanted into cirrhotic mice via the portal vein or tail vein. After 21 days, blood samples were collected for measurement of transaminase, bilirubin and albumin. The expression of fibrosis-associated genes, specifically procollagen – alpha 1 and integrin – beta1, were assessed using quantitative RT-PCR. The histopathology of the specimens was also evaluated using hematoxylin/eosin, Masson trichrome staining, and immunohistochemistry using collagen type 1 and alpha-SMA antibodies. Results: After 21 days, cirrhotic mice treated with UCB-MSCs showed recovery of bilirubin index, increase of liver albumin synthesis, inhibition of fibrosis-related gene expression (e.g. procollagen – alpha 1 and integrin – beta1), and remodeling of liver histology. From comparison of the different routes of transplantation, UCB-portal route was significantly more effective than UCB-tail route at reducing aspartate transaminase (AST) activity and bilirubin index (P<0.05), and inhibiting procollagen – alpha 1 and integrin – beta1 expression (P<0.05). UCB-MSCs from both transfusion routes showed accelerated improvement of liver histopathology. Conclusion: Therapeutic strategies using UCB-MSCs have proven to be promising for the treatment of liver cirrhosis. Injection of UCB-MSC via portal vein was more effective than tail vein for cirrhosis treatment.
Copyright (c) 2017 Trinh Van Le, Nam Hai Nguyen, Huy Quang Do, Huy Minh Le, Nhung Hai Truong
Concise review: Hematopoietic stem cell transplantation to treat insulin-dependent diabetes mellitus
Diabetes mellitus is a lifelong disease which causes negative effects on patient life. As a result of the disease, patients suffer from high blood sugar and the inability to obtain energy effectively from food. Diabetes mellitus can lead to life-threatening complications such as blindness, cardiovascular disease and diabetic coma. Diabetes can arise from defective insulin hormone production (usually related to type 1 diabetes mellitus or insulin-dependent diabetes mellitus (IDDM)) and/or defective insulin hormone function (related to type 2 diabetes mellitus). IDDM usually occurs in young people and can cause many serious health problems. There are several treatments which been investigated and applied in patients. Among them, stem cell therapy (especially hematopoietic stem cell therapy) has great potential to treat diabetes due to its many distinct advantages. The review will focus on diabetes mellitus, hematopoietic stem cells, and the novel hematopoietic stem cell therapy in diabetes mellitus type 1 treatment.
Copyright (c) 2017 Anh Thi-Van Bui, Phuc Van Pham
Conversion of human adipose derived stem cells into endothelial progenitor cells
Introduction: Endothelial cells (ECs) or endothelial progenitor cells (EPCs) are essential cells for blood vascular regeneration and vascular tissue engineering. However, the source of EPCs are limited. Indeed, these cells only existence with low rate at some tissues such as bone marrow, umbilical cord blood and peripheral blood. This study aimed to produce EPCs from direct reprogramming of adipose tissue-derived mesenchymal stem cells (ADSCs) by ETV2 transfection in vitro. Methods: ADSCs were isolated according to the published works. They were confirmed as mesenchymal stem cells (MSCs) with some characteristics included expression of CD44, CD73, CD90, negative of CD14, CD45, and HLA-DR; in vitro differentiation into adipocytes, and osteoblasts. ETV-2 mRNA was in vitro produced by commercial kit. ETV-2 mRNA molecules were transfected into ADSCs by Fugenes and Lipofectamine agents. These transfected cells were evaluated the expression of EPC properties included expression of CD31, VEGFR-2 in the cell surface by flow cytometry, immunocytochemistry, and in vitro vessel formation in the Matrigel. Results: The results showed that ETV-2 could transform the ADSCs from mesenchymal cell phenotype into endothelial cell phenotype with 10% transfected ADSCs expressing the CD31 in their surface, they also could form the vessel structure in vitro. Conclusion: Although the low efficacy of direct reprogramming, this study gave the new strategy to produce EPCs from the favorite cell sources as ADSCs.
Copyright (c) 2017 Van Hong Tran, Hoa Trong Nguyen, Phuc Van Pham
Concise review: Umbilical cord derived mesenchymal stem cell bank
Mesenchymal stem cells (MSCs) are the most promising stem cells for clinical applications. MSCs are widely used in disease treatment in some different countries. Recently, some MSC banks are developed to cryopreserve MSCs from umbilical cord tissues, adipose tissues, and bone marrow. This review aims to discuss some techniques, some advantages, as well as disadvantages of the umbilical cord, derived mesenchymal stem cell banking (UCMSCB). From 2010 to date, there are more than 10 UCMSCBs established in the world. There are two methods to isolate UCMSCs including tissue culture and single cell culture. Then they are cryopreserved in the liquid nitrogen for a long time. Although UCMSCBs can provide more the choice to store the MSCs from the umbilical cord, allogeneic MSC transplantation with high efficacy in disease treatment suggests that UCMSCBs should change with new approaches to use the cryopreserved samples.
Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion
More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment of human illnesses. More than five MSCs based stem cell drug products are approved in various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for six years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidence about the safety of expanded MSCs in clinical applications. However, the MSC quality should be strictly controlled during the in vitro MSC expansion.
Copyright (c) 2017 Vlassov V Salval, Yone Moto
An evolution of stem cell research and therapy in Viet Nam
Stem cell research is among the most exciting, attractive, and rapidly growing fields in biomedicine. Besides the popularity of stem cell research at the bench, stem cell therapy has become a bustling interest in the clinic and industry. In Vietnam, biomedical scientists have studied stem cells since 1995. From that time on, Vietnamese scientists have obtained significant achievements in stem cell research and therapy, especially with regards to stem cell therapy for disease treatment. This report aims to provide an overview of stem cell research and therapy from 1995 to date. Stem cell research activities were collected by questionnaire and analyzed based on publications and projects about stem cells in various databases, including Pubmed, Web of Science, Google Scholar, Embase, as well as from national scientific information. The results showed that stem cell research and therapy significantly increased from 2009 to date with greater publications on stem cells and clinical applications. With this growth rate, Vietnam is poised to continue developing in the stem cell industry. The potential goal for Vietnam is to advance as one of the countries in the Southeast Asian region and in the world that continues to push the frontier in stem cell research and therapy.
Copyright (c) 2018 Phuc Van Pham, Ngoc Bich Vu, Oanh Thuy Huynh, Mai Thi-Hoang Truong, Truc Le-Buu Pham, Long Thanh Dang, Ngoc Kim Phan
Expression of CD34 marker in the adipose tissue derived stem cells
Introduction: Adipose-derived stem cells (ADSCs) are considered as mesenchymal stem cells (MSCs). Indeed, they display all characteristics of MSCs that compliant with the minimal criteria of MSCs suggested by Domonici et al. (2006). However, some recent studies showed that ADSCs contain the subpopulation that was positive with CD34 marker – a marker of hematopoietic stem cells. This study aimed to analyze and determine the expression of CD34 marker in ten samples of ADSCs obtained from 10 donors. Methods: All ADSC samples were isolated and expanded according to the published previous protocols. They were confirmed as the MSCs with some markers and differentiation potential, excepting the CD34 expression. Then they were cultured and analyzed the expression of CD34 by flow cytometry at passage 3, 5, 7 and 9. Results: The results showed that expression of CD34 in ADSCs was different between donors and their passages that accounted from 1.21% to 23.38%. Conclusion: These results suggested that ADSCs are not ‘truly” MSCs like MSCs from bone marrow.
Copyright (c) 2018 Phuc Van Pham, Ngoc Bich Vu, Van Hong Tran
Mesenchymal stem cells transplantation reduces diabetic nephropathy
Diabetes mellitus is a metabolic disease in which the pancreas is unable to produce enough insulin due to the destruction of b -cells or the body does not utilize insulin properly. Continuous fluctuation of blood glucose levels is responsible for prolonged complications such as diabetic nephropathy (DN), diabetic retinopathy, or diabetic cardiomyopathy. Approximately, 20-30% of all diabetic patients face DN, which causes the formation of diabetic glomerular lesions and reduced glomerular filtration rate. In the case of renal failure, kidney transplantation is the only available therapy, however, it is expensive and almost unattainable due to unavailability of donors and host immune rejection. Stem cells are an alternative and attractive source of therapy because of their proliferative nature and the ability to produce distinct specialized cells. Mesenchymal stem cells (MSCs), which are derived from bone marrow, possess an anti-inflammatory property and the ability of selfrenewal and differentiation into a variety of specialized cells. MSCs are widely used to treat different diseases including DN and they have shown encouraging outcomes. This review provides details about the regenerative efficiency of using MSCs in treating diabetic nephropathy.
Copyright (c) 2019 Abeer Kazmi, Arsheema Kazmi, Wali Muhammad, Muhammad Azhar
Therapeutic role of bone marrow-derived stem cells and zinc sulfate for reduction of liver fibrosis
Introduction: Hepatic fibrosis is considered as the initial state of any chronic hepatic disease; progression causes accumulation of extracellular matrix (ECM) and develops into cirrhosis. In case of liver failure, transplantation was considered as the only suitable therapy but due to the hurdles in transplantation, therapy using stem cells was promoted. Mesenchymal stem cells (MSCs) are widely used for the treatment of a variety of diseases. Oxidative stress at the damage site causes poor MSC proliferation and engraftment. Thus, it is necessary to induce antioxidants with MSCs to enhance potency. Methods: To explore the therapeutic potential of zinc sulfate (ZnSO4) and MSCs on carbon tetra chloride (CCl4)-induced hepatic toxicity, 6-8 week-old female albino mice (BALB/c) were used. Initially, mice were infected with CCl4 and then intra-peritoneally injected with MSCs only, ZnSO4 only, or a combination of MSCs and ZnSO4. MSCs were isolated from femur and tibia of mice, and were cultured under control conditions. Results: The morphological results revealed that in contrast to MSC-only therapy, ZnSO4 enhanced the therapeutic potential of MSCs when administered to CCl4-injured mice. Biochemically, level of serum Alanine Transaminase (ALT) and total bilirubin was found to be significantly decreased in ZnSO4 + MSC transplanted mice. Histopathological examination also revealed that ZnSO4 + MSC transplantation induced a strong anti-apoptotic effect on CCl4-injured liver. Reverse transcription polymerase chain reaction (RT-PCR) detected a noteworthy anti-fibrotic effect of MSCs in the presence of ZnSO4, down-regulation of apoptotic marker (Bax), and up-regulation of anti-apoptotic (Bcl-xl) and hepatic (Albumin) markers. Conclusion: Thus, it was concluded that the presence of ZnSO4 reduced oxidative stress, enhanced the proliferation rate of MSCs, and significantly attenuated hepatic fibrosis.
Copyright (c) 2019 Arsheema Kazmi, Abeer Kazmi, Sulaiman Shams, Abdul Sajid, Khalid Khan
Isolation of cancer stem-like cells from hepatocellular carcinoma cell line HepG2 by methods of magnetic-activated cell sorting, spheroid culture, and anti-tumor drug-resistant selection: A primary evaluation
Introduction: Recently reported data have suggested that only a small subset of cancer cells possess the capability to initiate malignancies. These observations were based on investigation of cells within the primary tumors displaying a distinct surface marker pattern. CD133 marker is a putative hematopoietic and neuronal stem cell marker, which is also considered to be a tumorigenic marker in brain, prostate and liver. Recent studies have shown that a small population of CD133-positive cells, indeed, exists in human hepatocellular carcinoma (HCC) cell lines and primary HCC tissues. This study was aimed at isolating the cancer stem-like cells from hepatocellular carcinoma cell line HepG2 using three different methods: magnetic-activated cell sorting (MACS), spheroid culture (SC), and anti-tumor drug (ATD) resistant selection. Methods: HepG2 hepatocellular carcinoma cells were expanded to yield enough cells that could be used to isolate cancer stem-like cells by these three methods. For MACS, cancer stem-like cells were sorted using anti-CD133 monoclonal antibody. For the second method, cancer stem-like cells were enriched by selection of anti-tumor drug resistance property. Lastly, for the third method, three-dimensional (3D) culture was used to enrich for the cancer stem-like cells. The cells obtained by the three methods were expanded to obtain an adequate number of cells for confirmation of CD133 expression. Results: The expression of CD133+ cells in the three methods was found to be different. In the MACS method, the expanded CD133+ sorted cells cultured through 2 passages only contained 0.40 % CD133+ cells. In the 3D spheroid cell culture, of the population of cells there were 38.39 % that were CD133+ cells. Lastly, in the anti-tumor drug (doxorubicin at 150 nM) resistant selection, 66.22 % were CD133+ cells. Conclusion: This study shows that isolation of HepG2 derived CD133+ population by culture with doxorubicin (150 nM) yields the highest efficiency and purity of the 3 methods studied.
Copyright (c) 2020 Sinh Truong Nguyen, Luong Sy Nguyen, Thao Hoang Phuong Nguyen, Phuc Hong Vo, Nghia Minh Do, Kiet Dinh Truong, Phuc Van Pham
Ovarian cancer cells with CD133+ phenotype is more resistant against Ngai Bun Boesenbergia pandurata extract than original ovarian cancer cells
Introduction: Ovarian cancer is one of the most common cancers in women. Due to the difficulty in early detection and treatment of ovarian cancer, many research studies and clinical trials have been developed to discover more efficient therapies. Besides Western medicine, traditional medicine has gained increased interest as a research field with potential to lead to the production of marketable therapeutic products. With the diversity of tropical plants in Asia, traditional medicine has been very popular and has served as a traditional therapy for generations. The Ngai bun (Boesenbergia pandurata) root is used not only as a food spice but also in ethnomedicine. This study aimed to compare the anti-tumor activity of Boesenbergia pandurata root extract against ovarian cancer cells and CD133+ ovarian cancer cells that were enriched from the original ovarian cancer cells. Methods: Crude extract of Boesenbergia pandurata roots were prepared in two kinds of solvents (methanol and chloroform). The ovarian cancer cells OVP-10 were used in this study. The population of CD133+ ovarian cancer cells (CD133+OVP-10) were sorted from the OVP-10 cancer cells. Both OVP-10 cells and CD133+OVP-10 cells were treated with these crude extracts. Adiposederived stem cells (ADSCs) were used as control normal cells for all assays. The anti-tumor activity of extracts were evaluated based on the IC50 values. Results: Based on the IC50 index, the chloroform extract had an anti-tumor activity higher than that of methanol extract, on both OVP-10 and CD133+OPV-10 cells (IC50 of methanol and chloroform extracts were 330.1 +/- 16.9 ug/mL and 246.5 +/- 21.2 ug/mL, respectively, for OVP-10 cells; IC50 of methanol and chloroform extracts were 411.8 +/- 83.7 ug/mL and 307 +/- 9.2 ug/mL respectively, for CD133+OVP-10 cells). The results also showed that CD133+OVP-10 cells were more resistant to chloroform extract than were OVP-10 cells (307 +/- 9.2 mg/mL vs. 246.5 +/- 21.2 mg/mL, respectively, for CD133+OVP-10 vs. OVP-10 cells, p < 0.05). Conclusion: The chloroform extract of Boesenbergia pandurata roots displayed strong antitumor activity against ovarian cancer cells OVP-10 and CD133+OVP-10; the latter cells were found to be more resistant than the original ovarian cancer cells.
Copyright (c) 2020 Oanh Thi-Kieu Nguyen, Phuc Van Pham
Induced pluripotent stem cells are Japanese brand sources for therapeutic cells to pretrial clinical research
iPSCs are promising and have potential benefits for medical use, understanding human organogenesis, and cell therapy for advanced diseases. iPSCs are derived pluripotent cells which can further differentiate into functional human cell-lineages, such as neuronal, epithelial cells, cardiac cell, immune cell, and blood cells, etc. Thirteen years on, the discovery of iPSC has revolutionized the field of regenerative medicine, and also the number of clinical studies using iPSC has been growing rapidly worldwide. However, Japan is leading the race of iPSC-based studies and clinical trials due to government support. The Japanese government implemented the world’s fastest approval system and set to host first pretrial clinical studies using iPSC derived therapeutic products. Also, multinational companies of Japan are investing enormously in iPSC-based research for mobilization of iPSC-derived regenerative products to the research institution globally. This review presents an overview of iPSCs, potential benefits, commercialization of iPSC, iPSC-based pretrial clinical studies, and iPSC biobanking in Japan.
Using Defined Neural Cell Populations as a Possible Solution for Challenges in Neural Stem Cell Therapy
Neural stem cells exist in the mammalian nervous system. Despite extensive research to improve methods for isolation, propagation and differentiation of these cells, the clinical application of the in vitro expanded neural stem cells has remained challenging. These challenges include heterogeneity of neural stem cell progeny, limited neuronal cell yield both in number and phenotype, paucity of oligodendroglial cells, and predominant astroglial differentiation in vitro and after transplantation. Moreover, uncontrolled proliferation and tumorigenicity of the undifferentiated progeny possibly limit the clinical application of neural stem cells. Here, we propose using defined neural cell populations as a main solution.
Copyright (c) 2014 Progress in Stem Cell
Recent Progress in Stem Cell Chondrogenesis
Significant efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. To improve the clinical efficacy of stem cells for articular cartilage repair, understanding the factors and conditions that influence stem cell chondrogenesis in their lineage-specific differentiation and phenotypic stability of the cartilage formation following differentiation would be necessary. In this progress update, we discuss the use of the various sources of stem cells, induction factors including growth factors, oxygen tension and biomaterial scaffolds, and some of the cell-cell/matrix interactions and underlying mechanisms that regulate stem cell chondrogenesis towards stable cartilage formation.
Demons resurrected from Angels! What are or are not the molecular clues of the rising of the teratoma or teratocarcinoma from human amniotic stem cell?
Stem cell has great therapeutic potentials as it proliferates indefinitely, as well as gives rise to other cell type in our body. However, human pluripotent stem cell (hPSC) technology faces some obstacles associated with tumorigenicity and telomere shortening. And the risk of tumorigenicity of hPSC upon transplantation is one of the major hurdles, which must be overcome before hPSC based clinical practices. Interestingly, human amniotic stem cell (hASC) showed promising results by bypassing from the drawback. But, the important question is how hASC fully or partially escape from the progression of teratoma in severe combined immunodeficiency (SCID) mice, which remains unravel. It is decisive to comprehend the molecular mechanisms responsible for that of teratogenic and this non-teratogenic effect. Evidently, teratoma represents a critical line between stem cells, differentiation and tumorigenicis. And hASC typifies as a transitional stage between human embryonic stem cell (hESC) and adult stem cell. Hence, the study of hASC as a comparative model to reverse teratoma/teratocarcinoma formation and stem cell pluripotency to deciphering the molecular signals pathways promoting teratoma by hESC/hiPSC but not by hASC. Overall, learning the mechanisms of teratoma formation reversely by inducing in hASC could provide the knowledge that improves the tissue reconstitution potential from hESC and human induced PSC.
Copyright (c) 2015 Md. Shaifur Rahman, Madhuri Haque, S. M. Asaduzzaman
Adipose tissue derived stromal vascular fraction transplantation can recover spinal cord injury in mice
Introduction: Stem cell therapy is one of the most promising therapies for degenerative diseases and related injuries. Adipose tissue derived stem cells (ADSCs) exhibit some particular properties such as high production of paracrine factors. Indeed, ADSCs have been successfully used to treat diseases, including osteoarthritis, diabetic ulcer, etc. Methods: In this study, ADSCs were used to treat spinal cord injury (SCI) in a mouse model. Non-expanded ADSCs, from stromal vascular fractions (SVFs) isolated from both autologous and allogeneic adipose tissues, were injected into injured sites of mice at a specified dose. The SCI mouse model were generated by transection of spinal cord at vertebrae T8 - T10. After 1 week of transection, mice exhibiting completed SCI were divided into 4 groups: group 1 was control (mice without any treatment), group 2 was placebo (mice treated with platelet rich plasma (PRP)), group 3 was allogeneic SVF transplantation (mice treated with allogeneic SVFs), and group 4 was autologous SVF transplantation (mice treated with autologous SVFs). For the treatment groups, mice were transplanted with 20 µL of activated PRP or/and with 106 cells of SVF (allogeneic or autologous) into the injured position through laminectomy. The recovery of SCI was evaluated by locomotor test, sensory test and sensory-motor test at 5 weeks after transplantation. The histology of the spinal cord also was checked after 5 weeks. Results: The results showed that in all groups with PRP injected with or without SVFs, the inflammation was efficiently controlled. The glial scar as well as myelin defragmentation were clearly reduced. However, a significant improvement of BBB score was only recorded in mice transplanted with autologous SVFs. Conclusion: The results of our study show that autologous SVF transplantation in combination with PRP can be a promising therapy for SCI.
Copyright (c) 2016 Hau Thi-My Lam, Minh Nguyen-Thu Tran, Khoa Anh Bui, Thao Thi-Thu Le, Khanh Hong-Thien Bui, Ngoc Kim Phan, Phuc Van Pham
Autologous and allogeneic transplantation of adipose derived stem cells have similar efficacy for type 1 diabetes mellitus therapy in mouse models
Introduction: Type 1 diabetes mellitus (T1D) disease is caused by lesions or dysfunction of beta cells of pancreatic islets, causing less insulin to be secreted into the blood and thereby increasing glucose levels in the blood. In this study, we evaluated and compared the efficiency of treatment for T1D using autograft and allograft adipose-derived stem cells (ADSCs). Methods: ADSCs were collected from the belly of mice before they were injected using a single dose of streptozotocin (100 mg/kg) to induce T1D. T1D mice were intravenously injected with a dose of 2x106 ADSCs into the tail vein. Therapeutic efficacy was assessed by survival rate, blood glucose levels, serum insulin levels, histology and immunohistochemistry of pancreatic islets. Results: The results showed that both autograft and allograft transplantation of ADSCs demonstrated similarities in mortality rate, blood glucose level, blood insulin level, quantity and size of pancreatic islets. Both transplantations significantly improved T1D mice, which showed a decrease in mortality rate as well as blood glucose level, and increases in blood insulin level, quantity and size of pancreatic islets. Conclusion: The similar results suggest that both autologous and allogeneic transplantations of ADSCs are promising therapy for T1D treatment.
Copyright (c) 2016 Anh Nguyen-Tu Bui, Oanh Thi-Kieu Nguyen, Cong Le-Thanh Nguyen, Loan Thi-Tung Dang, Dung Phuong Nguyen, Phuc Van Pham, Ngoc Kim Phan