Navigating the labyrinth of cardiac regeneration

Lambers, Erin; Kume, Tsutomu

doi:10.1002/dvdy.24397

Cited by 13 publications

(7 citation statements)

References 120 publications

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“…BM mononuclear cells (BM-MNCs) are a heterogeneous cell population which includes, MSCs, hematopoietic cells, EPCs and others. BM-MNCs are easier to isolate than the component population and have been tested in numerous studies 110 , but in clinical trials appear to be less effective than MSCs 111 .…”

Section: Bone Marrow Mononuclear Cells (Bm-mncs)mentioning

confidence: 99%

Preclinical Studies of Stem Cell Therapy for Heart Disease

Tompkins

Balkan

Winkler

et al. 2018

Circulation Research

116

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As part of the TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) series to enhance regenerative medicine, here, we discuss the role of preclinical studies designed to advance stem cell therapies for cardiovascular disease. The quality of this research has improved over the past 10 to 15 years and overall indicates that cell therapy promotes cardiac repair. However, many issues remain, including inability to provide complete cardiac recovery. Recent studies question the need for intact cells suggesting that harnessing what the cells release is the solution. Our contribution describes important breakthroughs and current directions in a cell-based approach to alleviating cardiovascular disease.

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Section: Bone Marrow Mononuclear Cells (Bm-mncs)mentioning

confidence: 99%

Preclinical Studies of Stem Cell Therapy for Heart Disease

Tompkins

Balkan

Winkler

et al. 2018

Circulation Research

116

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“…The existence of progenitor populations in the adult heart has been the focus of many studies [ 75 ]. The criteria in the search for cardiac progenitor cells are that they should reside in the heart as a self-renewing pool of multipotent cells able to differentiate into the main cardiac lineages.…”

Section: Resident Cardiac Progenitors: Uncovering Residual Heart Dmentioning

confidence: 99%

“…Adult cardiomyocytes can also be obtained by derivation of other somatic cells, such as fibroblasts [ 75 , 106 ]. Cell reprogramming combines a dedifferentiation of fibroblasts to induced pluripotent stem (iPS) cells with directed differentiation to cardiomyocytes.…”

Section: Reprogrammed Cardiomyocytes: Recreating Heart Developmentmentioning

confidence: 99%

Cardiac Stem Cells in the Postnatal Heart: Lessons from Development

Aguilar-Sanchez

Michael

Pennings

2018

Stem Cells International

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Heart development in mammals is followed by a postnatal decline in cell proliferation and cell renewal from stem cell populations. A better understanding of the developmental changes in cardiac microenvironments occurring during heart maturation will be informative regarding the loss of adult regenerative potential. We reevaluate the adult heart's mitotic potential and the reported adult cardiac stem cell populations, as these are two topics of ongoing debate. The heart's early capacity for cell proliferation driven by progenitors and reciprocal signalling is demonstrated throughout development. The mature heart architecture and environment may be more restrictive on niches that can host progenitor cells. The engraftment issues observed in cardiac stem cell therapy trials using exogenous stem cells may indicate a lack of supporting stem cell niches, while tissue injury adds to a hostile microenvironment for transplanted cells. Engraftment may be improved by preconditioning the cultured stem cells and modulating the microenvironment to host these cells. These prospective areas of further research would benefit from a better understanding of cardiac progenitor interactions with their microenvironment throughout development and may lead to enhanced cardiac niche support for stem cell therapy engraftment.

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“…The latter strategy may avoid complications of cell transplantation including failure to engraft appropriately, short survival period, and cardiac arrhythmias (Lambers et al, 2016). In fact, several groups have succeeded in converting cardiac fibroblasts to functional cardiomyocytes with an efficiency of 7% to 20% by using a combination of multiple cardiac-lineage TFs (Gata4, Hand2, Mef2c, and Tbx5 or GHMT) (Qian et al, 2012; Song et al, 2012)(Fig.…”

Section: Regeneration In Non-mammalian Vertebrates and Other Mammamentioning

confidence: 99%

“…Notably, although iPSC differentiation and direct conversion are promising, the resulting cardiomyocytes, either in vitro or in vivo , still possess immature features of embryonic cardiomyocytes, namely higher proliferation rates, smaller and more rounded morphology lacking t-tubules and binucleation, and abnormal potassium currents that are responsible for arrhythmias (Lambers et al, 2016). …”

Section: Regeneration In Non-mammalian Vertebrates and Other Mammamentioning

confidence: 99%

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

Zheng

Zuo

2017

Hearing Research

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Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion. However, both processes are inefficient and incomplete, and decline with age. For direct lineage conversion in vivo in cochleae and in other systems, further improvement requires multiple factors, including transcription, epigenetic and trophic factors, with appropriate stoichiometry in appropriate architectural niche. Increasing evidence from other systems indicates that the molecular paths of direct lineage conversion may be different from those of normal developmental lineages. We therefore hypothesize that HC regeneration does not have to follow HC development and that epigenetic memory of supporting cells influences the HC regeneration, which may be a key to successful cochlear HC regeneration. Finally, we discuss recent efforts in viral gene therapy and drug discovery for HC regeneration. We hope that combination therapy targeting multiple factors and epigenetic signaling pathways will provide promising avenues for HC regeneration in humans with NIHL and other types of hearing loss.

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Navigating the labyrinth of cardiac regeneration

Cited by 13 publications

References 120 publications

Preclinical Studies of Stem Cell Therapy for Heart Disease

Preclinical Studies of Stem Cell Therapy for Heart Disease

Cardiac Stem Cells in the Postnatal Heart: Lessons from Development

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

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