Mesenchymal stem cells are derived from mature bone marrow and have the potential to differentiate down numerous mesenchymal lineages into differing mesodermal cell types, including adipocytes, chondrocytes or osteoblasts. Chondrocytes make up the cellular matrix of cartilage, referred to as endochondral ossification, becoming embedded in the cartilaginous matrix to maintain its integrity. While, osteoblasts secrete bone matrix, referred to as intramembranous ossification, for remodelling of the bone to re-establish shape and function. Thus mesenchymal stem cells are a significant factor in bone-healing as they denote the progenitors for both osteoblasts and chondrocytes (Aubin, 1998).
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His aim was to use mononuclear stem cells, they labelled as fibroblast colony-forming cells (FCFCs), to harvest clones of fibroblasts (Hall, 2005).
Figure 1. Images a-d, demonstrate fibroblast colonies cultured from monolayer bone marrow
(CIBA Foundation Symposium, 1973)
After 4 hours or so, he removed the nonadherent cells and consequently, the haematopoietic stem cells. Friedenstein described the adherent cells to appear heterogeneous, and spindle shaped, forming foci of two to four cells. These cells after approximately 2 to 4 days started to quickly multiply. The adherent cells developed even more consistent spindle-shaped appearance, after passage numerous times in culture. The capability of colonies to differentiate into what appeared to be small deposits of bone or cartilage became the most noteworthy and ground-breaking experimental result (Hall, 2005).
Figure 2. Diffusion chamber. Bone formation – fibroblasts formed from monolayer bone marrow culture (X20 magnification)
(CIBA Foundation Symposium, 1973)
Friedenstein’s preliminary discoveries were expanded on by numerous other researchers in the 1980s. In 1991, Caplan released his research on mesenchymal stem cells. He directed an assay to validate that marrow encompasses mesenchymal stem cells with the ability of bone and cartilage differentiation.
Figure 3. Diffusion chamber assay using marrow samples from mice.
Caplan’s methodology involved whole marrow is disrupted into 1-10 x 106 single cells and placed in a small diffusion chamber containing two Millipore filters allowing only body fluids to pass in and out of the chamber, however disallowing the mixture of host and mesenchymal cells. These chambers were then implanted an athymic mouse, into the peritoneal cavity, to act as an in vivo incubator. Mesenchymal cells rapidly divided and differentiated into cartilage and bone.
These key experimental findings popularised the study of mesenchymal stem cells as a potential orthopaedic therapy. Common for succeeding researchers was to focus on manipulating the endogenous osteogenic capabilities of mesenchymal stem cell and the increase of mesenchymal osteogenesis in bone restoration.
Since these primary finding we have seen the knowledge discovered applied to a variety of different experimentation and clinical trials, particularly to do with wound-healing. In 2004, Crevensten et al through an in vivo model, successfully regenerated the vertebral disc of rats with the injection of mesenchymal stem cells. Other health benefits of osteogenic mesenchymal stem cells were found in patients that were transplanted collagen gel comprising of bone marrow mesenchymal stem cells on full-thickness articular cartilage defects in the patellae. This resulted in a repair of that defect (Wakitani et al, 2004).
One of the largest areas of application of mesenchymal stem cells as oestrogenic progenitors is in the treatment for patients with degenerative bone...