Survival of iPSC-derived grafts within the striatum of immunodeficient mice: Importance of developmental stage of both transplant and host recipient

Tom, Colton M; Younesi, Shahab; Meer, Elana; Bresee, Catherine; Godoy, Marlesa; Mattis, Virginia B.

doi:10.1016/j.expneurol.2017.07.018

Cited by 5 publications

(1 citation statement)

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“…It is likely that the age of the transplant recipient will impact the degree of chimerism as the developing brain is more plastic to the integration of transplanted cells. One study observed that the neonatal mouse brain promoted the survival and migration of transplanted human cells when compared with adult mice . Multiple studies transplanting human fetal glial progenitor cells into demyelinated neonatal mice show the human cells integrate and out‐compete endogenous mouse glia, effectively creating a largely human glial network within the demyelinated mouse brain , whereas transplantation of other cell types into adult demyelinated animals results in limited engraftment .…”

Section: Discussionmentioning

confidence: 99%

Concise Review: Human-Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?

et al. 2019

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Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered preimplantation animal embryos eventually giving rise to fully developed human tissues and organs within the animal host for use in regenerative medicine. The ethical issues surrounding this method have caused the National Institutes of Health to issue a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal. To address this concern, we performed an in-depth review of the neural transplantation literature to determine how the integration of human cells into the nonhuman neural circuitry has altered the behavior of the host. Despite reports of widespread integration of human cell transplants, our review of 150 transplantation studies found no evidence suggestive of humanization of the animal host, and we thus conclude that, at present, concerns over humanization should not prevent research on blastocyst complementation to continue. We suggest proceeding in a controlled and transparent manner, however, and include recommendations for future research with careful consideration for how human cells may contribute to the animal host nervous system. STEM CELLS 2019;37:444-452 SIGNIFICANCE STATEMENTDue to a severe shortage of human organs and tissues, thousands of patients die each year due to an inability to procure organs for transplantation. Blastocyst complementation is a methodology that has the potential to generate large quantities of functioning human organs and tissues but is hindered by a National Institutes of Health moratorium on funding, citing concern over substantial human cell contribution to the brain of the animal. This review summarizes published, peer-reviewed studies on human-animal neural transplantation and suggests that this concern over neurological chimerism should not prevent research to continue in a controlled and transparent manner.

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Section: Discussionmentioning

confidence: 99%