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Title: The abundance of mesenchymal stem cells (MSCs) within the intramedullary cavities of long-bones & their potential mechanical translocation into systemic blood
Author: Cox, George Louis Daniel
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Aspiration of iliac-crest-bone-marrow (ICBM) is the most prevalent harvest technique for human mesenchymal-stem-cell (MSC) procurement Aspiration invariably yields low MSC numbers and cellular expansion is frequently required to obtain sufficient numbers of cells for purported MSC uses. Fatty-bone- marrow, resident within the intramedullary cavity of long-bones, is frequently accessed by the orthopaedic surgeon and may represent a richer source of MSCs - similar to other adipose tissues. Additionally, marrow fat may be mechanically translocated into systemic blood during orthopaedic procedures, and since MSCs are intimately associated with marrow fat, then the possibility arises that MSCs may circulate following orthopaedic manipulation. The intramedullary cavity was sampled by direct aspiration of long-bone fatty-bone-marrow (FBM) and by investigating the flow-through of the reamer-irrigator-aspirator (RIA) Synthes® (Paoli, USA). A comparative assessment was made of these MSCs with those from matched ICBM in tenms of enumeration, differentiation capacity and cultured phenotype. Solid-fractions from both intramedullary derived sources were further examined following collagenase digestion, Potential mechanical translocation of MSCs was investigated by venous-blood sampling during the intramedullary reaming of acute tibial-shaft fractures from sites proximal and distal to the filtering lung capillary-bed, Intramedullary sources contained MSCs with differentiation capacities, which were not inferior to those, derived from ICBM. Collagenase digestion of solid phases released large numbers of MSCs, although the greatest yield was from the high-volume, RIA-liquid fraction (mean = 115,000 MSCs). Occasional MSCs were isolated from femoral-vein blood (3 of 10 cases), proximal to lung, with none being detected distally. Cultured phenotypes were similar throughout the different MSC niches. Enzymatic digestion of solid FBM or concentration of the RIA flow-through both offer methods of isolating large yields of MSCs. The frequency of MSCs in the femoral circulation is extremely low, raising considerations regarding their blood-borne role.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available