Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Regenerative Injection Therapy (Prolotherapy)

Abstract

Adult mesenchymal stem cells (MSCs) obtainable from autologous bone marrow aspirates have generated tremendous interest in the medical and scientific communities in the last two decades and are currently being investigated by a of interested physicians for use in point-of-care stem cell therapies due to their great potential to differentiate into multiple cell lineages such as bone, cartilage, muscle, tendon, and nerve. However, as these stem cells are found in very low numbers in adult tissue, centrifugal concentration or expansion through in vitro culturing has been pursued to obtain higher numbers of efficacious regenerative therapeutic applications. More recently, some physicians and scientists have chosen to explore use for direct injection of un-fractionated, native whole bone marrow aspirate as a strategy in regenerative treatment regimes. This review examines the potential merits and disadvantages of using either concentrated and culture expanded MSCs versus native whole bone marrow aspirate as key proliferant in direct regenerative injection therapy (RIT). Results from a number of published investigations have clearly shown high potential of various deleterious effects on manipulating MSCs obtained from native bone marrow aspirate either by centrifugal forces or expansion through in vitro culturing; moreover, currently used centrifugal concentration techniques do not significantly concentrate MSCs from bone marrow aspirate, thus, defeating the purpose of this manipulative step. On the other hand, preliminary results and observations of using un-fractionated whole bone marrow injection for treatment of various musculoskeletal joint diseases (for example, osteoarthritic joints) suggest that the procedure is safe and potentially efficacious, with no known deleterious effects as yet reported.

Meta-Analysis and Evidence Base for the Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells in Knee Cartilage Repair: Methodological Guidelines and Quality Assessment

“…The heterogeneous composition of aspirate will synergistically foster the cartilage regeneration. In addition to avoiding any risk of rejection and any concerns about the lack of standardized protocols for stem cell preparation [44], most of included studies have aspirated the whole amount of autologous BM-MSCs from one insertion site in the iliac bone. Wakitani et al [27] and Centeno et al [23] aspirated half of the amount from the anterior superior iliac spine (ASIS) and the other half from the posterior superior iliac spine (PSIS).…”

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

“…One possible explanation for this finding is the relative paucity of the progenitor cells in the native, non-centrifuged bone marrow aspirate3233. However, some authors questioned the difference of the cellular components between native and centrifuged marrow aspirate2634. The native bone marrow aspirate was even proven to be superior to centrifuged bone marrow aspirate for the healing of meniscal lesions in a dog model35.…”

Low‐Intensity Ultrasound Upregulates the Expression of Cyclin‐D1 and Promotes Cellular Proliferation in Human Mesenchymal Stem Cells

“…[1][2][3] Therapeutic interventions with human mesenchymal stem cells (hMSCs) are limited by their low availability from in vivo sources such as bone marrow, where they represent a small fraction (0.001 to 0.01%) of the total nucleated cells. [4,5] Development of efficient in vitro MSC expansion protocols or clinically relevant strategies for in situ MSC recruitment and proliferation necessitates a better understanding of the factors impacting MSC proliferation. [6][7][8] Proliferation of hMSCs in response to chemical, biological or mechanical stimuli has been demonstrated.…”

“…Mesenchymal stem cells (MSCs) are a population of multipotent cells with self‐renewal capability, low immunogenicity, and are thus good candidates for applications in musculoskeletal tissue engineering; both in transplantable approaches that use MSC‐laden constructs or in vivo approaches that seek to recruit or home MSCs to the repair site . Therapeutic interventions with human mesenchymal stem cells (hMSCs) are limited by their low availability from in vivo sources such as bone marrow, where they represent a small fraction (0.001 to 0.01%) of the total nucleated cells …”