Stem cell induced cardiac regeneration: Fusion/mitochondrial exchange and/or transdifferentiation?

Song, Yao‐Hua; Pinkernell, Kai; Alt, Eckhard

doi:10.4161/cc.10.14.16513

Cited by 20 publications

(19 citation statements)

References 33 publications

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“…These myocytes might be derived from the stem cell population that has expressed Wt1 early during its life-span and resides in the heart. Alternatively, these cardiomyocytes might be the result of fusion of lineage positive mesenchymal cells with existing cardiomyocytes, a phenomenon also occurring during stem cell transplantation [53]. The observation that most of the myocytes do not have the characteristic adult cardiomyocyte shape and contain only one nucleus, renders this latter option unlikely.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Regeneration from Activated Epicardium

Wijk¹,

Gunst²,

Moorman³

et al. 2012

PLoS ONE

180

193

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In contrast to lower vertebrates, the mammalian heart has a very limited regenerative capacity. Cardiomyocytes, lost after ischemia, are replaced by fibroblasts. Although the human heart is able to form new cardiomyocytes throughout its lifespan, the efficiency of this phenomenon is not enough to substitute sufficient myocardial mass after an infarction. In contrast, zebrafish hearts regenerate through epicardial activation and initiation of myocardial proliferation. With this study we obtain insights into the activation and cellular contribution of the mammalian epicardium in response to ischemia. In a mouse myocardial infarction model we analyzed the spatio-temporal changes in expression of embryonic epicardial, EMT, and stem cell markers and the contribution of cells of the Wt1-lineage to the infarcted area. Though the integrity of the epicardial layer overlaying the infarct is lost immediately after the induction of the ischemia, it was found to be regenerated at three days post infarction. In this regenerated epicardium, the embryonic gene program is transiently re-expressed as well as proliferation. Concomitant with this activation, Wt1-lineage positive subepicardial mesenchyme is formed until two weeks post-infarction. These mesenchymal cells replace the cardiomyocytes lost due to the ischemia and contribute to the fibroblast population, myofibroblasts and coronary endothelium in the infarct, and later also to the cardiomyocyte population. We show that in mice, as in lower vertebrates, an endogenous, epicardium-dependent regenerative response to injury is induced. Although this regenerative response leads to the formation of new cardiomyocytes, their number is insufficient in mice but sufficient in lower vertebrates to replace lost cardiomyocytes. These molecular and cellular analyses provide basic knowledge essential for investigations on the regeneration of the mammalian heart aiming at epicardium-derived cells.

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Section: Discussionmentioning

confidence: 99%

Cardiac Regeneration from Activated Epicardium

Wijk¹,

Gunst²,

Moorman³

et al. 2012

PLoS ONE

180

193

View full text Add to dashboard Cite

show abstract

“…Although the results were encouraging, the mechanism is unclear. There are three possibilities for MSCs to recover cell or tissue function during the tissue regeneration process: (1) MSCs differentiated into the target function cells via appropriate induction conditions [1,17,18]; (2) Stem cells secreted trophic factors to stimulate the endogenous stem cells or restore the injured host cell function [2]; or (3) MSCs merge with the resident cells to recover the injured cell function [35,36]. In this study, we demonstrated that spermatogenically-differentiated BMSCs expressed integrin-β, c-kit, and GCNF in vitro and located at the basement of seminiferous tubule after implanted.…”

Section: Discussionmentioning

confidence: 99%

Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

Zhang

Liu

Peng

et al. 2014

IJMS

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Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

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“…In junction-formation mode, junctional proteins (e.g., connexins and cadherins) are distributed at the contact area between stem cells and cardiomyocytes: Connexins play an important role in electrical coupling, and cadherins do so for mechanical coupling [12]. Stem cells can also interact with cardiomyocytes by partial or full cell fusion process [13], [14]: Fused cells exhibit both stem cell and cardiomyocyte characteristics. A newly discovered mode of intercellular interaction between stem cells and cardiomyocytes is formation of thin-membrane channels (tunneling nanotubes).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Cardiomyocyte Interactions under Defined Contact Modes on Laser-Patterned Biochips

Yang

Liu

et al. 2013

PLoS ONE

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Understanding how stem cells interact with cardiomyocytes is crucial for cell-based therapies to restore the cardiomyocyte loss that occurs during myocardial infarction and other cardiac diseases. It has been thought that functional myocardial repair and regeneration could be regulated by stem cell-cardiomyocyte contact. However, because various contact modes (junction formation, cell fusion, partial cell fusion, and tunneling nanotube formation) occur randomly in a conventional coculture system, the particular regulation corresponding to a specific contact mode could not be analyzed. In this study, we used laser-patterned biochips to define cell-cell contact modes for systematic study of contact-mediated cellular interactions at the single-cell level. The results showed that the biochip design allows defined stem cell-cardiomyocyte contact-mode formation, which can be used to determine specific cellular interactions, including electrical coupling, mechanical coupling, and mitochondria transfer. The biochips will help us gain knowledge of contact-mediated interactions between stem cells and cardiomyocytes, which are fundamental for formulating a strategy to achieve stem cell-based cardiac tissue regeneration.

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Stem cell induced cardiac regeneration: Fusion/mitochondrial exchange and/or transdifferentiation?

Cited by 20 publications

References 33 publications

Cardiac Regeneration from Activated Epicardium

Cardiac Regeneration from Activated Epicardium

Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

Mesenchymal Stem Cell-Cardiomyocyte Interactions under Defined Contact Modes on Laser-Patterned Biochips

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