Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats.
Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor cells for mesenchymal tissues. These cells may also provide a potential therapy for bone repair. Our previous studies showed that MSC engineered with the gene for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were capable of differentiating into osteoblast lineage and inducing autologous bone formation in several animal models. Culturing individual MSC for autologous implantation, however, remains problematic. The number of human MSC with osteogenic potential decreases with age, and, in certain diseases, the patient's marrow may be damaged or the healthy cells reduced in number. In this study, we used rats with a femoral segmental defect to investigate whether allogeneic BMP-2 engineered MSC would facilitate bone healing. We show that BMP-2 engineered allogeneic MSC can repair critical bone defects to the same degree as rats treated with BMP-2 engineered autologous MSC, if the allogeneic group receives short-term treatment with immunosuppressant FK506. We also show that allogeneic gene transferred MSC are directly involved in bone repair, in addition to acting as gene deliverers.
Tsuchida
Hiroyuki
H
Department of Orthopaedic Surgery, Washington University School of Medicine, Barnes-Jewish Hospital at Washington University, One Barnes Hospital Plaza, STE 11300, St. Louis, MO 63110, USA.
Hashimoto
Junichi
J
Crawford
Eric
E
Manske
Paul
P
Lou
Jueren
J
D000818:Animals; D015519:Bone Density; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001861:Bone Regeneration; D002454:Cell Differentiation; D005260:Female; D005269:Femur / Q000166:cytology*; D015316:Genetic Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008648:Mesoderm / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology; D011859:Radiography; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation; D016559:Tacrolimus / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D014184:Transplantation, Homologous
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D016559:Tacrolimus