Concise Review: Heart-Derived Cell Therapy 2.0: Paracrine Strategies to Increase Therapeutic Repair of Injured Myocardium

Rafatian, Ghazaleh; Davis, Darryl R.

doi:10.1002/stem.2910

Cited by 19 publications

(17 citation statements)

References 70 publications

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“…With the astounding number of recent heart stem cell retractions, many have legitimately begun to question what contribution heart-derived (paracrine) therapeutics may ever provide to patient care [8]. To this, a reassuringly large body of work validates the therapeutic use of heart-derived cells but the future role of these cells is uncertain [45]. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium

et al. 2019

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BackgroundSerum-free xenogen-free defined media and continuous controlled physiological cell culture conditions have been developed for stem cell therapeutics, but the effect of these conditions on the relative potency of the cell product is unknown. As such, we conducted a head-to-head comparison of cell culture conditions on human heart explant-derived cells using established in vitro measures of cell potency and in vivo functional repair.MethodsHeart explant-derived cells cultured from human atrial or ventricular biopsies within a serum-free xenogen-free media and a continuous physiological culture environment were compared to cells cultured under traditional (high serum) cell culture conditions in a standard clean room facility.ResultsTransitioning from traditional high serum cell culture conditions to serum-free xenogen-free conditions had no effect on cell culture yields but provided a smaller, more homogenous, cell product with only minor antigenic changes. Culture within continuous physiologic conditions markedly boosted cell proliferation while increasing the expression of stem cell-related antigens and ability of cells to stimulate angiogenesis. Intramyocardial injection of physiologic cultured cells into immunodeficient mice 1 week after coronary ligation translated into improved cardiac function and reduced scar burden which was attributable to increased production of pro-healing cytokines, extracellular vesicles, and microRNAs.ConclusionsContinuous physiological cell culture increased cell growth, paracrine output, and treatment outcomes to provide the greatest functional benefit after experimental myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium

et al. 2019

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“…Their study demonstrated that the functional benefit of cardiac cell therapy is due to an acute inflammatory-based wound healing response that rejuvenates the mechanical properties of the infarcted area of the heart. In addition, the heart itself has stem cells, which can slowly selfrenew (Rafatian and Davis, 2018). A radioactive isotope study demonstrated that human cardiomyocytes gradually renew 1% of the cell population annually at the age of 25 years to 0.45% at the age of 75 years, which suggests that the heart has the limited ability of endogenous repair (Bergmann et al, 2009).…”

Section: Mechanism Of Stem Cell Therapymentioning

confidence: 99%

The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease

Liu

Han

Liang

et al. 2021

Front. Cell Dev. Biol.

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Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Stem cell transplantation has become a promising approach for the treatment of IHD in recent decades. It is generally recognized that preclinical cell-based therapy is effective and have yielded encouraging results, which involves preventing or reducing myocardial cell death, inhibiting scar formation, promoting angiogenesis, and improving cardiac function. However, clinical studies have not yet achieved a desired outcome, even multiple clinical studies showing paradoxical results. Besides, many fundamental puzzles remain to be resolved, for example, what is the optimal delivery timing and approach? Additionally, limited cell engraftment and survival, challenging cell fate monitoring, and not fully understood functional mechanisms are defined hurdles to clinical translation. Here we review some of the current dilemmas in stem cell-based therapy for IHD, along with our efforts and opinions on these key issues.

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“…Surprisingly, solely injecting the conditioned medium from these stem cells has shown restorative effects on the heart (Alibhai et al, 2018; Bollini et al, 2018). The restorative effects have been attributed to the secretion of paracrine factors, including EVs, from the stem cells (Alibhai et al, 2018; Bollini et al, 2018; Rafatian & Davis, 2018; Saha et al, 2019). Most EV studies in the cardiac area are based on 2D cultures or in vivo models with very few using 3D in vitro culture systems.…”

Section: Extracellular Vesicles From Organoids and 3d Culture Model Smentioning

confidence: 99%

Extracellular vesicles from organoids and 3D culture systems

Abdollahi

2020

Biotech & Bioengineering

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When discovered, extracellular vesicles (EVs) such as exosomes were thought of as junk carriers and a means by which the cell disposed of its waste material. Over the years, the role of EVs in cell communication has become apparent with the discovery that the nano‐scale vesicles also transport RNA, DNA, and other bioactive components to and from the cells. These findings were originally made in EVs from body fluids of organisms and from in vitro two‐dimensional (2D) cell culture models. Recently, organoids and other 3D multicellular in vitro models are being used to study EVs in the context of both physiologic and pathological states. However, standard, reproducible methods are lacking for EV analysis using these models. As a step toward understanding the implications of these platforms, this review provides a comprehensive picture of the progress using 3D in vitro culture models for EV analysis. Translational efforts and regulatory considerations for EV therapeutics are also briefly overviewed to understand what is needed for scale‐up and, ultimately, commercialization.

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Concise Review: Heart-Derived Cell Therapy 2.0: Paracrine Strategies to Increase Therapeutic Repair of Injured Myocardium

Cited by 19 publications

References 70 publications

Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium

Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium

The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease

Extracellular vesicles from organoids and 3D culture systems

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