MSCs as the Workhorse of Regenerative Medicine - Part II - Orthopaedic Roundup

MSCs truly are the Workhorse of Regenerative Medicine, and their use in Orthopaedic applications is where clinical translation was initially imagined.  However, the robust signaling activity of MSCs has widened the range of clinical indications to include cardiac, vascular, and neurological regeneration, as well as immunological applications (eg. GVHD, Chron’s disease), and more recently, cancer therapies.  

It is thus not surprising that MSCs were a strong component of the annual meeting of the Orthopaedic Research Society in New Orleans, LA in March.  We were fortunate enough to attend this conference and see the vast amount of work being conducted in the orthopaedic tissue engineering arena.  Not surprising to us, there were many presentations on the use of MSCs for musculoskeletal tissue repair and regeneration.  Below is some of the MSC research that caught our eye.

ORS 2014 abstracts can be downloaded here.

Orthopaedics, Image from: http://healthcare.utah.edu/orthopaedics/images/body_skeleton.png.

Tissue Engineered Periosteum Approaches to Heal Bone Allograft Transplants 

• Michael Hoffman, Benoit Lab, University of Rochester
• Transplantation of decellularized bone allografts seeded with both undifferentiated MSCs and MSCs differentiated to the osteogenic lineage lead to modulation of VEGF production and an increase in BMP2 production that resulted in an increase in torsional biomechanical graft host stability and rate of endochondral ossification compared to allograft alone and allograft seeded with undifferentiated MSCs alone.
• A related publication can be found here.

Anatomically Shaped, Vascularized Bone Grafts for Craniomaxillofacial Reconstruction

• Joshua Temple, Grayson Lab, Johns Hopkins University
• 3D printed porous scaffolds with correct anatomical features were successfully created to regenerate complex craniofacial deformities. Scaffolds containing adipose MSC aggregates formed extensive vascular networks as well as bone.  Implanted scaffolds demonstrated patent human vasculature and bone formation.
• A related publication can be found here.

Anatomic Hypertrophic Cartilaginous Grafts For Whole Bone Tissue Engineering

• Eamon Sheehy, Kelly Lab, Trinity College, Dublin
• Alginate, chitosan and fibrin hydrogels seeded with MSCs were investigated for bone formation through endochondral ossification.  While all constructs underwent robust chondrogenesis in vitro, alginate supported the greatest degree of endochondral bone formation in vivo, with the establishment of a hematopoietic marrow component with evidence of blood vessel infiltration. Subsequently, anatomically correct, MSC-seeded alginate hydrogels were used as the osseous layer of an engineered phalanx construct, which successfully underwent spatially regulated endochondral ossification in vivo.
• A related publication can be found here.

Inherent and Emergent Heterogeneity in Clonal Stem Cell Populations

• Brian Cosgrove, Mauck Lab, University of Pennsylvania
• Clonal MSC populations were compared to mixed, or non-selected MSC populations in terms of inherent heterogeneity.  Surprisingly, extensive biophysical heterogeneity exists both between clones and within clones.  This heterogeneity emerges very early in colony formation, persists in culture and is amplified with the addition of soluble factors to the culture medium.  Thus, heterogeneity in MSC populations has both inherent and emergent components.  Better understanding MSC heterogeneity and when it emerges could result in improved methods for successful MSC differentiation.

In Vivo Function and In Vitro Characterization of Tissue Engineered Intervertebral Discs Made with Human Mesenchymal Stem Cells

•  Katherine Hudson, Bonassar Lab, Cornell University
• Tissue engineered intervertebral discs were made using alginate and collagen seeded with MSCs to recreate the nucleus pulpous and annulus fibrosus.  In vitro, TE-IVDs treated with chondrogenic differentiation medium demonstrated increased stiffness and ability to pressurize compared to controls maintained in growth medium. In vivo, MSC containing discs maintained more hydration that punctured and degenerate discs.  In addition, MSC seeded discs maintained disc height for two weeks in vivo.
• A related publication can be found here. 

Standing room only at the MSC session at ORS.

One of the highlights of the conference was the special session dedicated to and titled “Mesenchymal Stem Cells”.  Frank Barry from Galway highlighted this session with a great overview of the MSC field.  It seemed like this was by far the most heavily attended session at the conference, and the take home message from the standing room only attendance is that there is tremendous interest in and promise of MSC use in orthopaedic research and development.

Clearly, MSC research in the orthopaedic space spans from understanding the basic mechanisms of MSC growth and differentiation to various application modalities of MSCs to treat a number of traumatic injuries and diseased states.  Findings presented at the ORS meeting demonstrated that MSCs aid in tissue repair via differentiation to intended lineages, through secretion of paracrine factors and through neovascularization.  We were very excited to see the emergence of 3D printing technologies incorporating MSCs from Hopkins, Cornell, and Utrecht (where you can now get a Master’s degree in Bioprinting!), and we look forward to continued discussion on understanding MSC heterogeneity and methods to better standardize MSC culture and clinical applications for Regenerative Medicine.

Keep an eye out for a future post on research presented at the Society for Biomaterials meeting that took place in Denver, CO.