Induced pluripotent stem cell‐derived gamete‐associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice

Kim, Eun Mi; Manzar, Gohar; Zavazava, Nicholas

doi:10.1111/imm.12722

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…In contrast, others have reported that mouse and human iPSC derivatives can be immunogenic in syngeneic or AU recipients and in an AU humanized mouse model, respectively 6–8 . Interestingly, it has also been shown that a host immune response (T-cell infiltration) associated with necrosis following transplantation of syngeneic iPSC, appears to be dependent on the antigenic profile of the transplant 6,9 . Recently, the more economically sustainable “MHC-paradigm”, i.e., matching the major histocompatibility complex (MHC) of both donor and recipient 10 , was tested in NHPs using retinal 11 or dopaminergic transplants 12 .…”

Section: Introductionmentioning

confidence: 99%

MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

et al. 2019

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Cell therapy products (CTP) derived from pluripotent stem cells (iPSCs) may constitute a renewable, specifically differentiated source of cells to potentially cure patients with neurodegenerative disorders. However, the immunogenicity of CTP remains a major issue for therapeutic approaches based on transplantation of non-autologous stem cell-derived neural grafts. Despite its considerable side-effects, long-term immunosuppression, appears indispensable to mitigate neuro-inflammation and prevent rejection of allogeneic CTP. Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to access CTP with enhanced immunological compatibility, ultimately reducing the need for immunosuppression. In the present work, we challenge this paradigm by grafting autologous, MHC-matched and mis-matched neuronal grafts in a primate model of Huntington’s disease. Unlike previous reports in unlesioned hosts, we show that in the absence of immunosuppression MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain.

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Section: Introductionmentioning

confidence: 99%

MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

et al. 2019

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“…During normal body function, different generations of cells must undergo processes that turn mature cells into stem cells ( 33 ). Although research relating to the induction of stem cells by acid has been questioned recently ( 34 ), there is no essential difference between the basic concept of this research and stem cell induction. The present study demonstrated that changes in the cellular environment may induce mature cells to become stem cells, although the identity of these specific environmental factors remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Induction of mesenchymal stem cell‑like transformation in rat primary glial cells using hypoxia, mild hypothermia and growth factors

Zhou

et al. 2020

Mol Med Rep

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The transformation of rat primary glial cells into mesenchymal stem cells (MSCs) is intriguing as more seed cells can be harvested. The present study aimed to evaluate the effects of growth factors, hypoxia and mild hypothermia on the transformation of primary glial cells into MSCs. Rat primary glial cells were induced to differentiate by treatment with hypoxia, mild hypothermia and basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Immunohistochemistry and western blotting were then used to determine the expression levels of glial fibrillary acidic protein (GFAP), nestin, musashi-1, neuron specific enolase (NSE) and neuronal nuclei (NeuN), in each treatment group. bFGF and EGF increased the proportion of CD44 + and CD105 + cells, while anaerobic mild hypothermia increased the proportion of CD90 + cells. The combination of bFGF and EGF, and anaerobic mild hypothermia increased the proportion of CD29 + cells and significantly decreased the proportions of GFAP + cells and NSE + cells. Treatment of primary glial cells with bFGF and EGF increased the expression levels of nestin, Musashi-1, NSE and NeuN. Anaerobic mild hypothermia increased the expression levels of Musashi-1 and decreased the expression levels of NSE and NeuN in glial cells. The results of the present study demonstrated that bFGF, EGF and anaerobic mild hypothermia treatments may promote the transformation of glial cells into MSC-like cells, and that the combination of these two treatments may have the optimal effect.

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“…Different combinations of transcription factors, such as Oct4, Sox2, Nanog, and Lin28 (68) or only Oct4 and Sox2 (69) can be also used to generate iPSCs. Despite the controversy on immunogenicity of autologous iPSCs (70)(71)(72)(73), devoid of ethical issues qualifies them as one of the most promising cell sources for cardiac tissue engineering.…”

Section: Pluripotent Stem Cellsmentioning

confidence: 99%

Engineering Human Cardiac Muscle Patch Constructs for Prevention of Post-infarction LV Remodeling

Wang

Serpooshan

Zhang

2021

Front. Cardiovasc. Med.

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Tissue engineering combines principles of engineering and biology to generate living tissue equivalents for drug testing, disease modeling, and regenerative medicine. As techniques for reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) and subsequently differentiating them into cardiomyocytes and other cardiac cells have become increasingly efficient, progress toward the development of engineered human cardiac muscle patch (hCMP) and heart tissue analogs has accelerated. A few pilot clinical studies in patients with post-infarction LV remodeling have been already approved. Conventional methods for hCMP fabrication include suspending cells within scaffolds, consisting of biocompatible materials, or growing two-dimensional sheets that can be stacked to form multilayered constructs. More recently, advanced technologies, such as micropatterning and three-dimensional bioprinting, have enabled fabrication of hCMP architectures at unprecedented spatiotemporal resolution. However, the studies working on various hCMP-based strategies for in vivo tissue repair face several major obstacles, including the inadequate scalability for clinical applications, poor integration and engraftment rate, and the lack of functional vasculature. Here, we review many of the recent advancements and key concerns in cardiac tissue engineering, focusing primarily on the production of hCMPs at clinical/industrial scales that are suitable for administration to patients with myocardial disease. The wide variety of cardiac cell types and sources that are applicable to hCMP biomanufacturing are elaborated. Finally, some of the key challenges remaining in the field and potential future directions to address these obstacles are discussed.

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Induced pluripotent stem cell‐derived gamete‐associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice

Cited by 4 publications

References 22 publications

MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

Induction of mesenchymal stem cell‑like transformation in rat primary glial cells using hypoxia, mild hypothermia and growth factors

Engineering Human Cardiac Muscle Patch Constructs for Prevention of Post-infarction LV Remodeling

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