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Fig. 1 | Stem Cell Research & Therapy

Fig. 1

From: “Mouse Clone Model” for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells

Fig. 1

Scheme of the “Mouse Clone Model” for stem cell transplantation. a One unique 2n mouse blastocyst. b 2n ESCs isolated and cultured from a. c 2n ESCs separated from b for microinjection. d Many 2n mouse two-cell embryos from the same or different mouse strains with a. e Many 4n one-cell embryos fused from d. f Many 4n blastocysts generated from e and injected with 2n ESCs from a to produce ESC mice by tetraploid complementation. g Mouse clone from 2n ESCs, theoretically all the same as each other. h Various tissue-specific stem cells isolated from g, using these stem cells to transplant g mice; theoretically transplanted into “themselves”. i Many induced iPSCs from g with different protocols [3, 4, 7]; theoretically, they should be the same as g, but for epigenetic reasons there are some differences between them. These iPSCs can be differentiated or directly transplanted into the mice of g. This step could identify “good” iPSC lines from “bad” iPSC lines based on the data of immune rejection and tumor formation, using the “good” iPSC lines which do not form tumor and do not have, or have less, immune rejection to generate iPSC mice. j First generation of iPSC mice generated from different iPSC lines from i by tetraploid complementation. This step can identify the “good” iPSC lines which can generate live mice from those which cannot. Combined with the data from the transplantation i, we can identify “good” iPSC lines, which can generate live mice, cannot form tumor, and do not have, or have less, immune rejection. k Various tissue-specific stem cells isolated from first-generation iPSC mice. These iPSC mice-derived tissue-specific stem cells can be differentiated or directly transplanted into the ESC-derived mice and iPSC-derived mice to investigate their efficacies according to the commonly agreed criteria. l Induced iPSC lines from first-generation iPSC mice. These lines are again investigated by transplanting into ESC mice, first-generation iPSC mice, and tetraploid complementation to produce the second generation of iPSC mice. m Keep on repeating to form a large group of different generations of iPSC mice, and isolate iPSCs and tissue-specific stem cells for transplantation. Using this model and strategy, a large clone of mice will be established from a unique 2n mouse blastocyst, for the investigation of stem cell therapy. ESC Embryonic stem cell, ICM Inner cell mass, iPSC Induced pluripotent stem cell

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