Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells

Abstract

For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40–80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 103-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs.

The elevated expression of calcitonin receptor by cells recruited into the endothelial layer and neo-intima of atherosclerotic plaque

“…Some of these populations arise from the subpopulations of mesenchymal (stromal) stem cells (Deans and Moseley 2000;Gronthos et al 2003;Jiang et al 2002). More recently, multi-potential adult progenitor cells (MAPCs) have been cultured in vitro and shown to proliferate through many cell cycles (Breyer et al 2006;SeraWni et al 2007;Tolar et al 2005). Furthermore, there is a growing realisation that some of these precursor cell populations may also be an important source of inWltrating cells in pathogenesis including tumour expansion (Fomchenko and Holland 2005), metastases (Kaplan et al 2005), atherosclerotic plaque (Xu et al 2003) and as a source of precursor cells for wound healing (Mori et al 2005).…”

Therapeutic pathways of adult stem cell repair

“…In circumstances of hematopoietic graft failure following HSC transplant, it is also feasible that adult stem cells such as MAPC that have hematopoietic reconstitution capacity, can be used directly without risk of GVHD complications. Indeed, this principle has been recently documented in reports from the Verfaillie and Weissman laboratories [126].…”

Mesenchymal Stem Cell Preparations—Comparing Apples and Oranges

“…MAPC have been shown to produce cells with characteristics of visceral mesoderm, neuroectoderm or endoderm [13,22]. Furthermore, MAPC of GFP-transgenic mice could give rise to hematopoietic cells that could be serially transplanted [23]. When injected into an early blastocyst, a single MAPC has been reported to contribute to the development of various tissues [11].…”