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Human-animal Neurological Chimeras: Humanized Animals Or Human Cells In An Animal?

Review

. 2019 Apr;37(4):444-452.

doi: 10.1002/stem.2971. Epub 2019 Jan 28.

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

Affiliations

  • PMID: 30629789
  • PMCID: PMC7167288
  • DOI: 10.1002/stem.2971

Complimentary PMC article

Review

Concise Review: Human-Animate being Neurological Chimeras: Humanized Animals or Human Cells in an Creature?

Andrew T Crane  et al. Stem Cells. 2019 Apr .

Free PMC article

Abstract

Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered preimplantation creature 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 accept caused the National Institutes of Wellness to effect a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal. To accost this concern, we performed an in-depth review of the neural transplantation literature to decide how the integration of human being cells into the nonhuman neural circuitry has contradistinct the behavior of the host. Despite reports of widespread integration of human prison cell transplants, our review of 150 transplantation studies institute no evidence suggestive of humanization of the animal host, and we thus conclude that, now, concerns over humanization should not prevent inquiry on blastocyst complementation to continue. We suggest proceeding in a controlled and transparent manner, yet, and include recommendations for hereafter enquiry with careful consideration for how human cells may contribute to the creature host nervous organization. Stem Cells 2019;37:444-452.

Keywords: Behavior; Blastocyst complementation; Cell transplantation; Chimera; Cognition; Stem cells.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

W.L. declared leadership position with Regenevida. The other authors indicated no potential conflicts of interest.

Figures

Figure 1.
Effigy 1.

Cartoon schematic of blastocyst complementation. Homo pluripotent stem cells grown in vitro are microinjected into genetically engineered porcine blastocysts which are then transferred to surrogate sows. The chimeric blastocysts develop to a fetal phase in which neural stem/progenitor cells tin can be harvested from the brain or to live-born animals where developed organs are processed for transplantation into patients.

Figure 2.
Figure 2.

Human cells used for preclinical or biomedical neurological inquiry. For scientific review, nosotros sampled a small fraction of the available peer-reviewed primary research articles in which human cells are transplanted into the CNS of mice, rats, and nonhuman primates. From these studies, a variety of cell lines were used which primarily fall into 3 categories: Embryonic stalk cell (ESC) derived, induced pluripotent stem cell (iPSC) derived and fetal-derived. These cells lines tin either be expanded then differentiated into neural stem/progenitor cells (NS/PC) or glial progenitors, or transplanted straight with minimal in vitro manipulation (fluorescent- or magnetic- activated cell sorting) and no in vitro expansion (primary fetal cells). Inside our review, an boosted category of NS/PC cell lines is identified, which includes directly conversion of somatic tissue to NS/PC and the teratocarcinoma-derived Ntera2/D1 prison cell line.

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