Xenotransplantation of human unrestricted somatic stem cells in a pig model of acute myocardial infarction

Gahremanpour, Amir; Vela, Deborah; Zheng, Yi; Silva, Guilherme V.; Fodor, William L.; Cardoso, Cristiano de Oliveira; Baimbridge, Fred; Fernandes, Marlos R.; Buja, L. Maximilian; Perin, Emerson C.

doi:10.1111/xen.12026

Cited by 10 publications

(3 citation statements)

References 36 publications

(71 reference statements)

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“…We observed some CD3 + T cells infiltrated in the injection area (supplemental online Fig. 4), a phenomenon that has also been observed in another study [53]. Second, it is not clear whether the therapeutic efficacy of this combined treatment would persist in chronic MI.…”

supporting

confidence: 60%

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Chang

Huang

Chen

et al. 2015

Stem Cells Translational Medicine

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This study using healthy human cord blood mononuclear cells (CB-MNCs) to treat myocardial infarction provides preclinical evidence that combined injection of hyaluronan and human CB-MNCs after myocardial infarction significantly increases cell retention in the peri-infarct area, improves cardiac performance, and prevents cardiac remodeling. Moreover, using healthy cells to replace dysfunctional autologous cells may constitute a better strategy to achieve heart repair and regeneration.

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supporting

confidence: 60%

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Chang

Huang

Chen

et al. 2015

Stem Cells Translational Medicine

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“…We found that once successful transplantation of human ADSCs and subsequent normal development of embryos were established, the donor cells in host tissues could be maintained for a long term (more than three months, data not shown). However, a dramatic reduction or even complete loss of donor cells with time extension was reported in several xenogeneic transplantation studies in animal models of rat, mouse, goat, and pig [ 9 , 33 – 35 ]. We speculate that the mature fish developed from the embryos injected with donor cells mistake these xenogeneic cells for their own components, and therefore maintained them for longer time than other animals.…”

Section: Discussionmentioning

confidence: 99%

Xenotransplantation of Human Adipose-Derived Stem Cells in Zebrafish Embryos

Jin

Zeng

et al. 2015

PLoS ONE

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Zebrafish is a widely used animal model with well-characterized background in developmental biology. The fate of human adipose-derived stem cells (ADSCs) after their xenotransplantation into the developing embryos of zebrafish is unknown. Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral vector system carrying a green fluorescent protein (GFP) reporter gene, and followed by detection of their cell viability and the expression of cell surface antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish embryos at 3.3–4.3 hour post-fertilization (hpf). Green fluorescent signal, the proliferation and differentiation of human ADSCs in recipient embryos were respectively examined using fluorescent microscopy and immunohistochemical staining. The results indicated that human ADSCs did not change their cell viability and the expression levels of cell surface antigens after GFP transduction. Microscopic examination demonstrated that green fluorescent signals of GFP expressed in the transplanted cells were observed in the embryos and larva fish at post-transplantation. The positive staining of Ki-67 revealed the survival and proliferation of human ADSCs in fish larvae after transplantation. The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31 expression was undetectable. Therefore, our results indicate that human ADSCs xenotransplanted in the zebrafish embryos not only can survive and proliferate at across-species circumstance, but also seem to maintain their undifferentiation status in a short term. This xenograft model of zebrafish embryos may provide a promising and useful technical platform for the investigation of biology and physiology of stem cells in vivo.

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“…In another study, pigs received human umbilical mesenchymal stem cells in artificial cardiac infarct area and were administered 5 mg/kg of cyclosporine orally twice a day, from the day before to 8 weeks after cell transplantation [15]. In a similar study, 10 mg/kg of cyclosporine was administered orally, twice a day from 3 days before to 8 weeks after the cell transplantation [16]. As a more sophisticated approach, cardiomyocyte sheet transplantation is being undertaken [17,18].…”

Section: Immunosuppressive Medications In Xenogeneic Transplantationmentioning

confidence: 99%

Controllable Immunosuppression in Pigs as a Basis for Preclinical Studies on Human Cell Therapy

Enosawa¹,

Kobayashi²

2020

Xenotransplantation - Comprehensive Study

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Along with a growing interest in regenerative medicine, pigs are becoming a popular model for preclinical studies on human cell therapy. Due to pharmaceutical species difference and inability to self-medicate, specific modification and care are necessary in immunosuppressive regimen for pigs. Here, we summarize recent literature on immunosuppression in pigs for experimental transplantation. Based on literature and our own experiences, a practical protocol has been proposed in this report. In early studies of allogeneic organ transplantation, recipient pigs were administered cyclosporine or tacrolimus, and mycophenolate mofetil at slightly higher dose than that in human cases, because of relatively poor effectiveness of the drugs in pigs. Steroids may be effective but sometimes can cause debilitating side effects. Cell transplantation studies follow the basic protocol, but it remains to be clarified whether the smaller graft mass, even if it is xenogeneic, requires the same scale of immunosuppression as organ transplantation. To obtain reliable results, the use of gastrostomy tube and blood trough level monitoring are highly recommended. Nonpharmaceutical immunosuppression such as thymic intervention and the use of severe combined immunodeficient pigs have also been discussed.

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Xenotransplantation of human unrestricted somatic stem cells in a pig model of acute myocardial infarction

Abstract: We conclude that human USSCs did not improve cardiac function in a pig model of AMI. Cell transplantation in a xenogeneic setting may obscure the benefits of stem cell therapy.

Cited by 10 publications

References 36 publications

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Xenotransplantation of Human Adipose-Derived Stem Cells in Zebrafish Embryos

Controllable Immunosuppression in Pigs as a Basis for Preclinical Studies on Human Cell Therapy

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