Cellular Bone Matrices Lack Sufficient Clinical Data in Promoting Bone Proliferation.
Mesenchymal Stem Cells (MSCs) and multipotent adult progenitor cells (MAPCs) are undifferentiated stem cells. MAPCs are believed to be more primitive than MSCs and can differentiate into endoderm, mesoderm, or ectodermal tissue, while MSCs differentiate into mesodermal tissue alone (e.g. bone, cartilage, fat, tendon, and other connective tissues). MSCs normally constitute between 0.001% to 0.01% of nucleated bone marrow cells. Iliac crest aspiration produces between one and five MSCs per half a million nucleated cells.
MSCs and MAPCs differentiate into various connective tissue types depending upon cytokine influence (proteins that stimulate cells -such as growth factors) and local environment (e.g. spatial density, bioactive nutrients, mechanical forces, surface interactions)
Allogenic MSCs and MAPCs are alleged to be immunologically privileged, but this is based upon in vitro evidence alone and is refuted by a number of vivo studies, all of which demonstrate both humoral and cellular immune response (see “Immunogenicity of Allogenic Mesenchymal Stem Cells,” Shu et al, J. Cell. Mol. Med. Vol 16, No 9, 2012 pp. 2094-2103 and Ankrum, J.; Ong, J.F.; Karp, J.M. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat. Biotechnology. 2014, 32, 252–260.)
Allogenic MSCs and MAPCs are not in and of themselves osteoproliferative, it is only when they differentiate into osteoblasts that osteoid (i.e. unmineralized collagen-proteoglycan matrix) and alkaline phosphatase (enzyme utilized to mineralize osteoid) are capable of being generated (i.e. bone formation). These allogenic osteoblasts (i.e. those derived from allogenic MSCs) are neither immunologically privileged or evasive (neither in vitro or in vivo).
CBMs are offered by a variety of companies, deriving their cellular component separately from bone marrow and adipose tissue
Various CBMs are offered by a variety of companies as substitutes for autograft or acellular allograft, yet none of these CBM offerings have been demonstrated to be more effective in the production of bone in non-industry sponsored clinical studies
There is no compelling evidence that CBMs containing MSCs or MAPCs are more likely to produce bone than demineralized bone matrix and/or allogenic lyophilized cancellous bone, in either animal (“Mesenchymal Stem Cell Concentration and Bone Repair: Potential Pitfalls from Bench to Bedside,” Cuomo et al, J Bone Joint Surg Am. 2009;91:1073-83) or clinical studies (see systematic literature review studies cited below).
“Cell Based Therapies as Compared to Autologous Bone Grafts for Spinal Arthrodesis,” Khashan et al, Spine. 2013; 38(21): 1885 – 1891 – UCSF systematic literature review study – “The currently available evidence is insufficient to support the use of MSCs or BMA combined with synthetic or allograft materials as a substitute or supplementary graft to autologous bone graft.”
“Cellular Bone Matrices: Viable Stem Cell-Containing Bone Graft Substitutes,” Skovrij et al, Spine Journal 2014 Nov. 1; 14(11): 2763 – 2772 – Mount Sinai literature review study – “Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive… With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.”
“Stem Cells and Spinal Fusion,” Stephan et al, International Journal of Spine Surgery. Vol. 15, Supplement 2021, S94 – S103 – Cedars-Sinai literature review study – “Cell-based allografts and the optimization of their use have yet to be fully elucidated. Further studies are necessary to determine the efficacy of MSCs with different osteoconductive scaffolds and growth/osteogenic differentiation factors.”
