Human Mesenchymal Stem Cells Derived from Bone Marrow Display a Better Chondrogenic Differentiation Compared with Other Sources

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into several mesodermal lineages. These cells have been isolated from various tissues, such as adult bone marrow, placenta, and fetal tissues. The comparative potential of these cells originating from different tissues to differentiate into the chondrogenic lineage is still not fully defined. The aim of our study was to investigate the chondrogenic potential of MSCs isolated from different sources. MSCs from fetal and adult tissues were phenotypically characterized and examined for their differentiation capacity, based on morphological criteria and expression of extracellular matrix components. Our results show that both fetal and adult MSCs have chondrogenic potential under appropriate conditions. The capacity of bone marrow-derived MSCs to differentiate into chondrocytes was reduced on passaging of cells. MSCs of bone marrow origin, either fetal or adult, exhibit a better chondrogenesis than fetal lung- and placenta-derived MSCs, as demonstrated by the appearance of typical morphological features of cartilage, the intensity of toluidine blue staining, and the expression of collagen type II, IX, and X after culture under chondrogenic conditions. As MSCs represent an attractive tool for cartilage tissue repair strategies, our data suggest that bone marrow should be considered the preferred MSC source for these therapeutic approaches.

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

“…Recent findings showed a decreased chondrogenic potential in aged human male MSCs but no decline in female MSCs [41]. Another recent report on fetal and adult human MSCs showed similar adipogenic and osteogenic differentiation, but age caused diminished cartilage ECM formation [8].…”

Human Fetal and Adult Bone Marrow-Derived Mesenchymal Stem Cells Use Different Signaling Pathways for the Initiation of Chondrogenesis

“…However, MSCs exhibit significant heterogeneity and variation in potency both within and between patients [8]. In addition, adult MSCs undergo replicative senescence, resulting in a decrease in their prevalence, proliferation rate, and differentiation capacity [9,10]. This variability and tendency to senesce is severely limiting and poses significant implications for advancements in the use of MSC-based therapies for cartilage repair.…”

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

“…BMP6 therapy increased the differentiation of stem cells towards chondrocytes and osteocalcin positive osteoblasts [48,116,123] in the bone (Fig. 3).…”

“…(a) At the endosteal surface BMP2 affects both osteoclasts and osteoblasts with a net outcome of downregulation of Runx2, collagen I and Wnt signaling [75]; at the periosteum BMPs stimulate differentiation of precursor cells (green) into osteoblasts (orange); and in surrounding muscle cells (myoblasts, pericytes and vascular satellite cells) BMPs upregulate Id genes and form new osteoblasts and prechondrocytes to form cartilage and new bone around the cortical layer from which the new bone spreads into the medullar cavity. (b) As shown in patients with high tibial osteotomy and a fibular defect, BMP7 (Osigraft) stimulates bone formation from periosteum (P) and surrounding muscles (M) spreading endostealy at six and ten weeks to rebuild the cortical bone (CB) at one year following implantation (modified from [109]) Uniqueness and exceptionality of BMP6 BMP6 has specific effects in its ability to convert stem cells to cartilage and bone forming cells [13,48,116]. BMP6 and several other BMP family members are produced and released by BMSC and hematopoietic stem cells (HSC) which both constitute the stem cell niche of the bone marrow [117].…”

“…This is certainly an unexpected finding given that BMP6 shares numerous receptor binding and signaling characteristics with BMP7 [28,122]. Such a resistance of BMP6 to inactivation by BMP antagonist(s) might, in addition, be ascribed to BMP receptor type I binding affinity and explain why large amounts of BMP7 are needed in commercially used BMP-based bone devices for a successful bone formation and repair in monkeys and patients [116,123,124].…”