Therapeutic potential of adult bone marrow-derived mesenchymal stem cells in prostate cancer bone metastasis.
OBJECTIVE
Current evidence indicates that an osteoblast lesion in prostate cancer is preceded by osteolysis. Thus, prevention of osteolysis would reduce complications of bone metastasis. Bone marrow-derived mesenchymal stem cells have the ability to differentiate into osteoblast and produce osteoprotegerin, a decoy receptor for the receptor activator for nuclear factor kappaB ligand, naturally. The present study examined the potential of unmodified mesenchymal stem cells to prevent osteolytic bone lesions in a preclinical mouse model of prostate cancer.


METHODS
The human prostate cancer cell line PC3 was implanted in tibiae of severe combined immunodeficient mice. After establishment of the tumor, either unmodified or genetically engineered mesenchymal stem cells overexpressing osteoprotegerin was injected at the site of tumor growth. The effects of therapy were monitored by bioluminescence imaging, micro-computed tomography, immunohistochemistry, and histomorphometry.


RESULTS
Data indicated significant (P < 0.001) inhibition of tumor growth and restoration of bone in mice treated with unmodified and modified mesenchymal stem cells. Detailed analysis suggested that the donor mesenchymal stem cell inhibited tumor progression by producing woven bone around the growing tumor cells in the tibiae and by preventing osteoclastogenesis.


CONCLUSIONS
Overcoming the limitation of the number of mesenchymal stem cells available in the bone can provide significant amelioration for osteolytic damage without further modification.
Chanda
Diptiman
D
Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA.
Isayeva
Tatyana
T
Kumar
Sanjay
S
Hensel
Jonathan A
JA
Sawant
Anandi
A
Ramaswamy
Girish
G
Siegal
Gene P
GP
Beatty
Matthew S
MS
Ponnazhagan
Selvarangan
S
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D045744:Cell Line, Tumor; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D013977:Tibia / Q000473:pathology; D055114:X-Ray Microtomography / Q000379:methods
D053244:Osteoprotegerin