Osteogenic ability of rat bone marrow concentrate is at least as efficacious as mesenchymal stem cellsin vitro

Abstract

Cell therapy using bone marrow concentrate (BMC) or purified and expanded mesenchymal stem cells (MSCs) has been shown to have a promising osteogenic capacity. However, few studies have directly compared their relative osteogenic ability. The aim of this study was to compare the osteogenic ability of BMC isolated by density gradient centrifugation with bone marrow‐derived MSCs in vitro using the cells of 3‐month‐old Sprague–Dawley rats. The isolated cells were seeded onto 24‐well plates (1 × 105 cells/well) and cultured in control growth media, osteogenic media with dexamethasone, or media without dexamethasone (which simulated the in vivo tissue environment). Alkaline phosphatase activity at week 2, osteocalcin using quantitative real‐time polymerase chain reaction at week 4, and Alizarin red staining at week 4 were evaluated. In the osteogenic media with dexamethasone, BMC showed equivalent (osteocalcin) or even greater (Alizarin red staining) osteogenic ability compared to MSCs, suggesting that cross‐talk among various cells in the BMC leads to greater osteogenesis. Furthermore, in the osteogenic media without dexamethasone, BMC showed equivalent (osteocalcin) or a trend for greater (Alizarin red staining) bone formation than MSCs alone. Our results suggest that BMC has at least comparable bone regeneration potential to MSCs. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2500–2506, 2019

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

“…The immunosuppression of effector functions, preventing the development of immunological diseases, is possible due to the communication of innate and adaptive immune cells with MSCs via inflammatory cytokines e.g., IL17, IL-6, IFN-γ and growth factors e.g., hepatocyte growth factor (HGF), prostaglandin E2 (PGE2), transforming growth factor-β (TGF-β) [95]. Furthermore, the inhibitory effects of MSCs on the proliferation of T cells are dependent on the expression of interleukin 17 (IL- 17), such that in mice, IL-17-induced mesenchymal stem cells had their homing ability enhanced, resulting in the prolonged survival time of allogeneic skin grafts through suppressed immune recognition [96]. Interleukin IL-6 stimulates the proliferation and survival of T cells, in contrast to interferon-γ (IFN-γ), which suppress the proliferation of regulatory T cells and other immune cells [97].…”

“…The therapeutic evaluation of stem cells in allogenic models requires the evaluation of animal models prior to and during treatment as a means of assessing the homing properties of cells in response to local transplantation. The usefulness of cells with osteogenic potential generates clinically encouraging cell-based treatments applied to complex fractures in bone defects and bone diseases like osteonecrosis, osteoarthritis, osteosclerosis, ovariectomy-induced osteoporosis and a few genetic disorders, including hypophosphatasia and achondroplasia [17,160]. Even though bone marrow stromal cells (BMSCs), and adipose tissue-derived stem cells (ASCs) have been demonstrated to hold promising osteogenic capacity; only recently a growth has been observed in the number of applications utilizing live BMSCs and ASCs in preclinical research.…”

“…In addition, in all cases of patients suffering from long-bone pseudoarthrosis, complete bone consolidation was achieved when treated with allogenic cancellous bone grafts combined with iliac crest-derived autologous BM-MNCs [164]. Interestingly, comparison of osteogenic ability of rat bone marrow concentrate (BMC) and mesenchymal stem cells suggests that BMC has higher osteogenic potential, due to the cross talk of hematopoietic stem cells, mesenchymal stem cells and osteoprogenitors, which does not occur in therapies based solely on MSCs [17]. Bone marrow aspirate used in the treatment of osteonecrosis during the minimally invasive decompression of the femoral head halted the progression of the disease and resulted in pain relief [165].…”

“…Such modifications to osteocyte-adipocyte balance could serve to supplement future treatments of osteoporosis, as well as other related diseases [2]. Moreover, a 2019 study suggested that bone marrow concentrate may hold potential for more effective treatment than MSCs alone, due to crosstalk between MSCs and other progenitor cells [17].…”

“…An improvement in the understanding of osteogenic stem cell differentiation, including the factors, signalling pathways and small molecules involved in this process, could result in novel therapeutic opportunities of bone disease treatment. Moreover, current techniques could be enhanced through the analysis of cellular communication in skeletal tissue during repair and remodelling, in both normal and pathological conditions [17,18]. Hence, this review summarizes the newest findings on the potential and current research associated with the clinical applications of cells with osteogenic differentiation potential.…”