Telephone: 501-686-8745; Fax: 501-686-6442
Article first published online: 24 FEB 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 2, pages 263–273, February 2011
How to Cite
Li, X., Ling, W., Pennisi, A., Wang, Y., Khan, S., Heidaran, M., Pal, A., Zhang, X., He, S., Zeitlin, A., Abbot, S., Faleck, H., Hariri, R., Shaughnessy, J. D., van Rhee, F., Nair, B., Barlogie, B., Epstein, J. and Yaccoby, S. (2011), Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone. STEM CELLS, 29: 263–273. doi: 10.1002/stem.572
Author contributions: X.L.: performed in vitro and in vivo studies, analyzed and interpreted the data, and wrote the paper; W.L.: performed in vitro and in vivo studies; Y.W.: performed in vivo studies; A.P. and S.K.: performed in vitro studies; J.S.: performed gene expression profiling and analyzed and interpreted the data; J.E.: helped design the experimental studies and analyzed and interpreted the data; B.B., F.v.R., and B.N.: provided patients' materials and interpreted the data; M.H., A.P., X.Z., S.H., A.Z., S.A., H.F., and R.H.: manufactured and provided PDAC, characterized PDAC cellular, and molecular properties and interpreted the data; S.Y.: performed research, conceptualized the work, analyzed and interpreted the data, and wrote the paper.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 23, 2010.
- Issue published online: 24 FEB 2011
- Article first published online: 24 FEB 2011
- Accepted manuscript online: 23 NOV 2010 12:03PM EST
- Manuscript Accepted: 12 NOV 2010
- Manuscript Received: 16 JUL 2010
- Celgene Cellular Therapeutics. Grant Number: CA-093897
- National Cancer Institute. Grant Numbers: CA55819, CA113992
- Bone disease;
- Mesenchymal stem cells
Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into nonmyelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. STEM CELLS 2011;29:263–273