Ex vivo expansion and in vivo infusion of bone marrow-derived Flk-1+CD31-CD34- mesenchymal stem cells: feasibility and safety from monkey to human.
Flk-1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) are multipotent cells with extensive proliferation ability and immunomodulatory function. On the basis of our previous work showing their potential application in tissue engineering and immune diseases, we designed a preclinical and Phase I trial to evaluate the feasibility and safety of intravenous infusion of these cells after ex vivo expansion. Rhesus monkey and human Flk-1(+)CD31(-)CD34(-) MSCs were isolated from bone marrow and passaged a maximum of six passages. Karyotype analysis showed Flk-1(+)CD31(-)CD34(-) MSCs remained normally diploid within six passages of expansion. Expanded cells were transplanted into rhesus monkeys and human volunteers, respectively. During the infusion of these cells, the life signs of the recipients were normal. Laboratory tests for blood, bone marrow, kidney, and liver function were conducted and no significant changes were observed before and after cell infusion. Identification of the sry sequence from the male donor in female recipients showed that allogeneic rhesus Flk- 1(+)CD31(-)CD34(-) MSCs were capable of homing to and establishing residence within the recipients' bone marrow. No significant changes were observed in lymphocyte cell subpopulation before and after infusion. These result showed that Flk-1(+)CD31(-)CD34(-) MSCs have no obvious side effects after intravenous administration, encouraging investigators to perform further studies in stem cell therapy.
Liu
Lihui
L
Department of Hematology, Affiliated Hospital of Academy of Military Medicine Science, Beijing, PR China.
Sun
Zhao
Z
Chen
Bin
B
Han
Qin
Q
Liao
Lianmin
L
Jia
Mingyue
M
Cao
Ying
Y
Ma
Jie
J
Sun
Qiyun
Q
Guo
Mei
M
Liu
Zeyuan
Z
Ai
Huisheng
H
Zhao
Robert Chunhua
RC
D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D046528:Chimerism; D033481:Chromosomes, Mammalian / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D000882:Haplorhini / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007621:Karyotyping; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D014182:Transplantation, Autologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D018952:Antigens, CD34; D000954:Antigens, Surface; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2