Donor cell-derived osteopoiesis originates from a self-renewing stem cell with a limited regenerative contribution after transplantation

Massimo Dominici, Roberta Marino, Valeria Rasini, Carlotta Spano, Paolo Paolucci, Pierfranco Conte, Ted J. Hofmann, Edwin M. Horwitz

Research output: Contribution to journalArticlepeer-review

Abstract

In principle, bone marrow transplantation should offer effective treatment for disorders originating from defects in mesenchymal stem cells. Results with the bone disease osteogenesis imperfecta support this hypothesis, although the rate of clinical improvement seen early after transplantation does not persist long term, raising questions as to the regenerative capacity of the donor-derived mesenchymal progenitors. We therefore studied the kinetics and histo-logic/anatomic pattern of osteopoietic en-graftment after transplantation of GFP-expressing nonadherent marrow cells in mice. Serial tracking of donor-derived GFP + cells over 52 weeks showed abundant clusters of donor-derived osteoblasts/osteo-cytes in the epiphysis and metaphysis but not the diaphysis, a distribution that paralleled the sites of initial hematopoietic en-graftment. Osteopoietic chimerism decreased from approximately 30% to 10% by 24 weeks after transplantation, declining to negligible levels thereafter. Secondary transplantation studies provided evidence for a self-renewing osteopoietic stem cell in the marrow graft. We conclude that a transplantable, primitive, self-renewing osteopoietic cell within the nonadherent marrow cell population engrafts in an endosteal niche, like hematopoietic stem cells, and regenerates a significant fraction of all bone cells. The lack of durable donor-derived osteopoi- esis may reflect an intrinsic genetic program or exogenous environmental signaling that suppresses the differentiation capacity of the donor stem cells.

Original languageEnglish
Pages (from-to)4386-4391
Number of pages6
JournalBlood
Volume111
Issue number8
DOIs
Publication statusPublished - Apr 15 2008

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'Donor cell-derived osteopoiesis originates from a self-renewing stem cell with a limited regenerative contribution after transplantation'. Together they form a unique fingerprint.

Cite this