Normal bone marrow hematopoietic stem cell reserves and normal stromal cell function support the use of autologous stem cell transplantation in patients with multiple sclerosis

Abstract

Summary:Bone marrow (BM) stem cell reserves and function and stromal cell hematopoiesis supporting capacity were evaluated in 15 patients with multiple sclerosis (MS) and 61 normal controls using flow cytometry, clonogenic assays, long-term BM cultures (LTBMCs) and enzymelinked immunosorbent assays. MS patients displayed normal CD34 þ cell numbers but a low frequency of colony-forming cells (CFCs) in both BM mononuclear and purified CD34 þ cell fractions, compared to controls. Patients had increased proportions of activated BM CD3 þ /HLA-DR þ and CD3 þ /CD38 þ T cells that correlated inversely with CFC numbers. Patient BM CD3 þ T cells inhibited colony formation by normal CD34 þ cells and patient CFC numbers increased significantly following immunomagnetic removal of T cells from BMMCs, suggesting that activated T cells may be involved in the defective clonogenic potential of hematopoietic progenitors. Patient BM stromal cells displayed normal hematopoiesis supporting capacity indicated by the CFC number in the nonadherent cell fraction of LTBMCs recharged with normal CD34 þ cells. Culture supernatants displayed normal stromal derived factor-1 and stem cell factor/kit ligand but increased flt-3 ligand levels. These findings provide support for the use of autologous stem cell transplantation in MS patients. The low clonogenic potential of BM hematopoietic progenitors probably reflects the presence of activated T cells rather than an intrinsic defect.

Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

“…Transplantation of autologous MSCs in NOD mice was accompanied by development of soft tissue and visceral tumors, which were not observed with the transfer of allogeneic MSCs (24). A concern with MSCs from patients with autoimmune disease has been the potential for decreased immunomodulatory capacity, although recent studies reported that MSCs from patients with multiple sclerosis and rheumatoid arthritis had normal cell surface and molecular phenotype and ability to support hematopoiesis (50,51). It is not clear whether the capacity of these MSCs is as robust as allogeneic MSCs for immunomodulation or whether these cells require additional manipulation ex vivo to augment their immunomodulatory capacity.…”

Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from patients with systemic sclerosis

“…Similarly, in patients with rheumatoid arthritis, a defect in the MSC-mediated support of haematopoiesis was attributed to an increased production of tumour necrosis factor α 27. The same group has shown that stromal cells from patients with multiple sclerosis display instead normal in vitro haematopoiesis supporting capacity 35. These in vitro data question the feasibility and suitability of such patients with AD to undergo autologous stem cell (CD34+) transplantation.…”

Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia

“…A population of activated T cells in patients' BM is the main source of IFN-g and FasL [75,76]. These cells exhibit major myelosuppressive properties, as demonstrated in coculture experiments, in which patients' BM CD3 + T cells significantly inhibit autologous or allogeneic normal granulocytic progenitor cell growth [77]. In addition, we have recently shown that most CIN patients display an oligoclonal/ monoclonal pattern within the BM and/or peripheral blood CD8 + cells [76].…”