Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion.
OBJECTIVE
The human bone marrow contains mesenchymal stem cells capable of differentiating along multiple mesenchymal cell lineages. Using a non-human primate model, we sought to determine whether the systemic infusion of baboon-derived mesenchymal stem cells was associated with toxicity and whether these cells were capable of homing to and persisting within the bone marrow.


METHODS
Five baboons (Papio anubis) were administered lethal irradiation followed by intravenous autologous hematopoietic progenitor cells combined with either autologous (n = 3) or allogeneic (n = 2) mesenchymal stem cells that had been expanded in culture. In four of these baboons, the mesenchymal stem cells were genetically modified with a retroviral vector encoding either the enhanced green fluorescent protein gene (n = 3) or the human placental alkaline phosphatase gene (n = 1) for tracking purposes. A sixth animal received only intravenous gene marked autologous mesenchymal stem cells but no hematopoietic stem cells or conditioning irradiation.


RESULTS
Following culture, baboon mesenchymal stem cells appeared morphologically as a homogeneous population of spindle-shaped cells that were identified by the monoclonal antibodies SH-3 and SH-4. These cells did not express the hematopoietic markers CD34 or CD45. Baboon mesenchymal stem cells isolated from primary culture were capable of differentiating along both adipogenic and osteogenic lineages. There was no acute or chronic toxicity associated with the intravenous infusion of mesenchymal stem cells. In all five recipients of gene marked mesenchymal stem cells, transgene was detected in post-transplant bone marrow biopsies. In two animals receiving autologous mesenchymal stem cells, including the one non-conditioned recipient, transgene could be detected over 1 year following infusion. In one recipient of allogeneic gene marked mesenchymal stem cells, transgene was detected in the bone marrow at 76 days following infusion.


CONCLUSIONS
These data demonstrate that baboon mesenchymal stem cells: 1) are not associated with significant toxicity when administered intravenously, 2) are capable of homing to the bone marrow following intravenous infusion, and 3) have the capacity to establish residence within the bone marrow for an extended duration following systemic administration.
Devine
S M
SM
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. sdevine@uic.edu
Bartholomew
A M
AM
Mahmud
N
N
Nelson
M
M
Patil
S
S
Hardy
W
W
Sturgeon
C
C
Hewett
T
T
Chung
T
T
Stock
W
W
Sher
D
D
Weissman
S
S
Ferrer
K
K
Mosca
J
J
Deans
R
R
Moseley
A
A
Hoffman
R
R
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000737:chemistry; D002469:Cell Separation; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000276:immunology; D010215:Papio; D016133:Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection; D019076:Transgenes
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D004274:DNA, Recombinant; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D000469:Alkaline Phosphatase; D017493:Leukocyte Common Antigens