Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells

Abstract

Mesenchymal stem cells (MSCs) are a population of pluripotent cells within the bone marrow microenvironment defined by their ability to differentiate into cells of the osteogenic, chondrogenic, tendonogenic, adipogenic, and myogenic lineages. We have developed methodologies to isolate and culture-expand MSCs from human bone marrow, and in this study, we examined the MSC's role as a stromal cell precursor capable of supporting hematopoietic differentiation in vitro. We examined the morphology, phenotype, and in vitro function of cultures of MSCs and traditional marrow-derived stromal cells (MDSCs) from the same marrow sample. MSCs are morphologically distinct from MDSC cultures, and flow cytometric analyses show that MSCs are a homogeneous cell population devoid of hematopoietic cells. RT-PCR analysis of cytokine and growth factor mRNA in MSCs and MDSCs revealed a very similar pattern of mRNAs including IL-6, -7, -8, -11, -12, -14, and -15, M-CSF, Flt-3 ligand, and SCF. Steady-state levels of IL-11 and IL-12 mRNA were found to be greater in MSCs. Addition of IL-1alpha induced steady-state levels of G-CSF and GM-CSF mRNA in both cell preparations. In contrast, IL-1alpha induced IL-1alpha and LIF mRNA levels only in MSCs, further emphasizing phenotypic differences between MSCs and MDSCs. In long-term bone marrow culture (LTBMC), MSCs maintained the hematopoietic differentiation of CD34+ hematopoietic progenitor cells. Together, these data suggest that MSCs represent an important cellular component of the bone marrow microenvironment.

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

“…This finding was in concurrence with previous studies reporting that MSCs, derived from patients who had undertaken chemotherapeutic treatments for various different malignancies, produce normal levels of hemopoietic support in vitro [6,8,41]. The role of MSC damage in engraftment kinetics in vivo is unknown; however, it is known that MSCs can produce a number of early-acting cytokines that maintain HSC in quiescence or promote their self-renewal and also a variety of interleukins and cytokines which act on more mature hematopoietic progenitors [33,34].…”

“…CD44 is an adhesion molecule that plays a critical role in normal hematopoiesis [31,32], and it is the stromal microenvironment consisting of stromal cells and extracellular matrix that is thought to regulate and support the future fate of stem cells and committed progenitors along specific lineages [33][34][35]. The role and function of CD44 have been extensively studied on the surface of hemopoietic cells, however, much less so when concerning its presence on MSCs.…”

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

“…Bone marrow mesenchymal stem cells (MSCs) are currently among the best characterized adult stem cells (Majumdar et al, 1998;Pittenger et al, 1999) isolated from various tissue sources such as fat, muscle, and bone (Jiang et al, 2002b;Sottile et al, 2002;Zuk et al, 2002). These cells are able to differentiate into bone, fat, cartilage, muscle tissue, and neurons (Mackay et al, 1998;Reyes et al, 2001;Sekiya et al, 2004;Woodbury et al, 2000) and were ultimately reported in almost all cell lineages (Jiang et al, 2002;Krause et al, 2001).…”

Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

“…It has been approved have the capability to support expansion of hematopoietic stem cells (HSC) through expressing cytokines and reconstructing hematopoietic microenvironment [13,14]. Furthermore, preliminary investigation has revealed that MSC are not immunogenic although weekly expressing class II major histocompatibility complex (MHC-II) [15,16].…”