Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

Ji, Seung Taek; Kim, Hyunyun; Yun, Jisoo; Chung, Joo Seop; Kwon, Sang‐Mo

doi:10.1155/2017/3945403

Cited by 51 publications

(33 citation statements)

References 114 publications

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“…VEGF is an angiogenic and pro‐regenerative growth factor (Arsic et al, ). VEGF protects MSCs from cellular stress, supports myoblast growth, angiogenesis, and tissue regeneration (Ji, Kim, Yun, Chung, & Kwon, ). The expression of VEGF continuously increased over time after Day 5 (Figure ) suggesting the regenerative potential of MSCs also increased.…”

Section: Discussionmentioning

confidence: 99%

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Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

Talovic

Patel

Schwartz

et al. 2019

J Tissue Eng Regen Med

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Volumetric muscle loss (VML) injuries are irrecoverable due to a significant loss of regenerative elements, persistent inflammation, extensive fibrosis, and functional impairment. When used in isolation, previous stem cell and biomaterial‐based therapies have failed to regenerate skeletal muscle at clinically relevant levels. The extracellular matrix (ECM) microenvironment is crucial for the viability, stemness, and differentiation of stem cells. Decellularized‐ECM (D‐ECM) scaffolds are at the forefront of ongoing research to develop a viable therapy for VML. Due to the retention of key ECM components, D‐ECM scaffolds provide an excellent substrate for the adhesion and migration of several cell types. Mesenchymal stem cells (MSCs) possess regenerative and immunomodulatory properties and are currently under investigation in clinical trials for a wide range of medical conditions. However, a major limitation to the use of MSCs in clinical applications is their poor viability at the site of transplantation. In this study, we have fabricated spherical scaffolds composed of gelatin and skeletal muscle D‐ECM for the adhesion and delivery of MSCs to the site of VML injury. These spherical scaffolds termed “gelloids” supported MSC survival, expansion, trophic factor secretion, immunomodulation, and myogenic protein expression in vitro. Future studies would determine the therapeutic efficacy of this approach in a murine model of VML injury.

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Section: Discussionmentioning

confidence: 99%

“…VEGF protects MSCs from cellular stress, supports myoblast growth, angiogenesis, and tissue regeneration (Ji, Kim, Yun, Chung, & Kwon, 2017). The expression of VEGF continuously increased over time after MSCs are considered to be immunoprivileged and do not elicit an immune response in their new host (Ankrum, Ong, & Karp, 2014).…”

Section: Discussionmentioning

confidence: 99%

Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

Talovic

Patel

Schwartz

et al. 2019

J Tissue Eng Regen Med

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“…Ischemic heart damage disrupts this homeostatic balance, which leads to a series of cellular events including apoptosis, necrosis, various inflammatory responses, and remodeling processes resulting in scar formation, ventricular stiffness, and altered contractibility [ 3 ]. Though medical and surgical treatments such as pharmacotherapy, percutaneous coronary intervention (PCI), and surgical management can significantly improve patient outcomes and reverse viable ischemic tissue, no current treatment is able to create new contractile tissue or regenerate lost myocardium [ 4 ]. Heart transplantation is the only definitive treatment for the ischemic heart failure that results after MI; however, the procedure involves significant risk and donors are limited [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Use of Stem Cells for Myocardial Infarction

Madigan

Atoui

2018

Bioengineering

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Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative processes do exist in the myocardium—tissue previously thought not to possess regenerative properties—the use of stem cells has emerged as a promising therapeutic approach with high expectations. The literature describes the use of cells from various sources, categorizing them as either embryonic, induced pluripotent, or adult/tissue stem cells (mesenchymal, hematopoietic, skeletal myoblasts, cardiac stem cells). Many publications show the successful use of these cells to regenerate damaged myocardium in both animal and human models; however, more studies are needed to directly compare cells of various origins in efforts to draw conclusions on the ideal source. Although numerous challenges exist in this developing area of research and clinical practice, prospects are encouraging. The following aims to provide a concise review outlining the different types of stem cells used in patients after myocardial infarction.

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“…Another strategy to bolster the therapeutic potential of hMSCs is priming/preconditioning the hMSCs-which exposes them to physical treatments (e.g., hypoxia and heat shock), pharmacological agents, growth factors, distinct types of biomaterials, modified culture conditions, or other various molecules, including microRNAs-in vitro before transplantation into the hearts (11)(12)(13)(14)(15). Previous studies of the underlying mechanisms of the priming effects reported that hMSCs receiving these priming applications had short-term memory and remembered a priming stimulus, even after relocating to new environments, and shifted their phenotype in therapeutically desirable directions (14,16).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

Cited by 51 publications

References 114 publications

Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

Therapeutic Use of Stem Cells for Myocardial Infarction

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

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