title: Human placenta-derived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone.
abstract: 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.
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors: Xin
authors: X
authors: Li
authors: Wen
authors: W
authors: Ling
authors: Angela
authors: A
authors: Pennisi
authors: Yuping
authors: Y
authors: Wang
authors: Sharmin
authors: S
authors: Khan
authors: Mohammad
authors: M
authors: Heidaran
authors: Ajai
authors: A
authors: Pal
authors: Xiaokui
authors: X
authors: Zhang
authors: Shuyang
authors: S
authors: He
authors: Andy
authors: A
authors: Zeitlin
authors: Stewart
authors: S
authors: Abbot
authors: Herbert
authors: H
authors: Faleck
authors: Robert
authors: R
authors: Hariri
authors: John D
authors: JD
authors: Shaughnessy
authors: Frits
authors: F
authors: van Rhee
authors: Bijay
authors: B
authors: Nair
authors: Bart
authors: B
authors: Barlogie
authors: Joshua
authors: J
authors: Epstein
authors: Shmuel
authors: S
authors: Yaccoby
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D001862:Bone Resorption / Q000517:prevention & control*; D002454:Cell Differentiation; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010012:Osteogenesis / Q000502:physiology*; D010014:Osteolysis / Q000517:prevention & control* / Q000628:therapy*; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D011817:Rabbits