TY - JOUR
T1 - In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells
AU - Amabile, Giovanni
AU - Welner, Robert S.
AU - Nombela-Arrieta, Cesar
AU - D'Alise, Anna Morena
AU - Di Ruscio, Annalisa
AU - Ebralidze, Alexander K.
AU - Kraytsberg, Yevgenya
AU - Ye, Min
AU - Kocher, Olivier
AU - Neuberg, Donna S.
AU - Khrapko, Konstantin
AU - Silberstein, Leslie E.
AU - Tenen, Daniel G.
PY - 2013/2/21
Y1 - 2013/2/21
N2 - Lineage-restricted cells can be reprogrammed to a pluripotent state known as induced pluripotent stem (iPS) cells through overexpression of 4 transcription factors. iPS cells are similar to human embryonic stem (hES) cells and have the same ability to generate all the cells of the human body, including blood cells. However, this process is extremely inefficient and to date has been unsuccessful at differentiating iPS into hematopoietic stem cells (HSCs). We hypothesized that iPS cells, injected into NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ immunocompromised (NSG) mice could give rise to hematopoietic stem/progenitor cells (HSPCs) during teratoma formation. Here, we report a novel in vivo system in which human iPS cells differentiate within teratomas to derive functional myeloid and lymphoid cells. Similarly, HSPCs can be isolated from teratoma parenchyma and reconstitute a human immune system when transplanted into immunodeficient mice. Our data provide evidence that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications.
AB - Lineage-restricted cells can be reprogrammed to a pluripotent state known as induced pluripotent stem (iPS) cells through overexpression of 4 transcription factors. iPS cells are similar to human embryonic stem (hES) cells and have the same ability to generate all the cells of the human body, including blood cells. However, this process is extremely inefficient and to date has been unsuccessful at differentiating iPS into hematopoietic stem cells (HSCs). We hypothesized that iPS cells, injected into NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ immunocompromised (NSG) mice could give rise to hematopoietic stem/progenitor cells (HSPCs) during teratoma formation. Here, we report a novel in vivo system in which human iPS cells differentiate within teratomas to derive functional myeloid and lymphoid cells. Similarly, HSPCs can be isolated from teratoma parenchyma and reconstitute a human immune system when transplanted into immunodeficient mice. Our data provide evidence that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications.
UR - http://www.scopus.com/inward/record.url?scp=84874438241&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-06-434407
DO - 10.1182/blood-2012-06-434407
M3 - Article
SN - 0006-4971
VL - 121
SP - 1255
EP - 1264
JO - Blood
JF - Blood
IS - 8
ER -