scholarly journals Challenges and Limitations of Strategies to Promote Therapeutic Potential of Human Mesenchymal Stem Cells for Cell-Based Cardiac Repair

2021 ◽  
Vol 51 (2) ◽  
pp. 97
Author(s):  
Thi Van Anh Bui ◽  
Ji-Won Hwang ◽  
Jung-Hoon Lee ◽  
Hun-Jun Park ◽  
Kiwon Ban
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Cardiac Repair

scholarly journals In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction

2021 ◽  
Vol 22 (3) ◽  
pp. 1449
Author(s):  
Woo-Sup Sim ◽  
Bong-Woo Park ◽  
Kiwon Ban ◽  
Hun-Jun Park
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Genetically Engineered ◽  
Cardiac Repair ◽  
Therapeutic Platform

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.

scholarly journals Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media

2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Sunghoon Jung ◽  
Krishna M. Panchalingam ◽  
Lawrence Rosenberg ◽  
Leo A. Behie
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Culture Media ◽  
Human Mesenchymal Stem Cells ◽  
Efficient Production ◽  
Serum Free ◽  
Medium Development ◽  
Current Cell ◽  
Free Media

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.

scholarly journals Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction

2021 ◽  
Vol 9 ◽  
Author(s):  
Thora Bjorg Sigmarsdottir ◽  
Sarah McGarrity ◽  
James T. Yurkovich ◽  
Óttar Rolfsson ◽  
Ólafur Eysteinn Sigurjónsson
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Cell Lineage ◽  
Human Mesenchymal Stem Cells ◽  
Metabolic Model ◽  
Metabolic Function ◽  
Metabolic States ◽  
Initial Discovery ◽  
Genome Scale

Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs.

Adiponectin Improves Therapeutic Efficacy of Mesenchymal Stem Cells by Enhancing Their Engraftment and Survival in Peri-infarct Myocardium Through AMPK Pathway

2020 ◽  
Author(s):  
Xiaqiu Tian ◽  
Xiao-Song Qian ◽  
Hong Wang ◽  
Yue-Jin Yang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Cardiac Function ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Cardiac Repair ◽  
Heart Catheterization ◽  
Cell Marker ◽  
Ampk Pathway

Abstract Background: Poor viability of transplanted mesenchymal stem cells (MSCs)within the ischemic heart has limited their therapeutic potential for cardiac repair. We have recently demonstrated that adiponectin (APN) inhibits the apoptosis of MSCs under hypoxia and serum-deprivation conditionsin vitro. This study investigated whether APN could promote the survival of MSCs in vivoand further contribute to cardiac repair after acute myocardial infarction (AMI), via the adenosine monophosphate-activated protein kinase(AMPK)pathway. Methods: Rats were randomized into six groups: the Sham, AMI control, and 4 other groups that were subjected to AMI followed by treatment with MSCs, APN, APN + MSCs and APN + MSCs + AMPK inhibitor. MSCs labeled with CM-Dil were injected through the jugular vein in 24 hours post AMI. At 4-week after AMI, engraftment of MSCs to the peri-infarct myocardium was evaluated. Cardiac function was assessed using echocardiography and left heart catheterization. Apoptosis and fibrosis were measured with TUNEL and Masson’s trichrome staining. H&E staining and immunohistochemistry against CD 68 and CD 206 were performed to assess the infiltration of inflammatory cells. Expressions of inflammatory cytokines were determined with ELISA. Immunostaining against smooth muscle cell marker α-smooth-muscle actin (α-SMA) and endothelial cell marker CD31 antibodies were performed to assess arteriogenesis and angiogenesis. Results: APN treatment significantly enhanced the engraftment and survival rate of transplanted MSCs accompanied by markedly improved cardiac function and decreased infarct size at 4-week after AMI. Combined administration of APN and MSCs markedly suppressed inflammatory response, specifically promoted shift of infiltrated macrophages to anti-inflammatory phenotype.Combined administration of APN and MSCs also significantly inhibited cardiomyocytes apoptosis, while increased arteriogenesis and angiogenesis in the peri-infarct myocardium when compared with MSCs transplantation alone. These protective effects of APN were associated with AMPK phosphorylation, which were almost completely reversed by AMPK pathway inhibitor. Conclusions: Our results demonstrated that APN could improve the survival and therapeutic efficacy of transplanted MSCs after AMI through AMPK activation.Our study suggests the potential application of APN for improvement of stem cell-based heart repair and regeneration.

scholarly journals In vivo priming of human mesenchymal stem cells with hepatocyte growth factor–engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair

2020 ◽  
Vol 6 (13) ◽  
pp. eaay6994 ◽  
Author(s):  
Bong-Woo Park ◽  
Soo-Hyun Jung ◽  
Sanskrita Das ◽  
Soon Min Lee ◽  
Jae-Hyun Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Therapeutic Potential ◽  
Cardiac Repair ◽  
Vascular Regeneration ◽  
Cardiac Patch ◽  
Hepatocyte Growth

The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

scholarly journals Retinal Lineage Therapeutic Specific Effect of Human Orbital and Abdominal Adipose-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Bryan Krief ◽  
Shira Weisthal Algor ◽  
Itay Nakdimon ◽  
Ayala Elhikis ◽  
Moshe Benhamou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Subcutaneous Fat ◽  
Human Mesenchymal Stem Cells ◽  
Specific Effect ◽  
Photoreceptor Layer ◽  
Retinal Tissue ◽  
Embryonic Origin

Retinal degenerative diseases are one of the main causes of complete blindness in aged population. In this study, we compared the therapeutic potential for retinal degeneration of human mesenchymal stem cells derived from abdominal subcutaneous fat (ABASCs) or from orbital fat (OASCs) due to their accessibility and mutual embryonic origin with retinal tissue, respectively. OASCs were found to protect RPE cells from cell death and were demonstrated to increase early RPE precursor markers, while ABASCs showed a raise in retinal precursor marker expression. Subretinal transplantation of OASCs in a mouse model of retinal degeneration led to restoration of the RPE layer while transplantation of ABASCs resulted in a significant restoration of the photoreceptor layer. Taken together, we demonstrated a lineage-specific therapeutic effect for either OASCs or ABASCs in retinal regeneration.

scholarly journals Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1536 ◽  
Author(s):  
Norlaily Mohd Ali ◽  
Lily Boo ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
Dilan A. Satharasinghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Culture Condition ◽  
Therapeutic Potential ◽  
Age Groups ◽  
Human Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Differentiation Potential

Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC) is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (<30 years) and aged (>60 years) donors were expanded under hypoxic (5% O2) and normal (20% O2) culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO) and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia) > young (normoxia) > old aged (hypoxia) > old aged (normoxia).

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