Bone marrow aspirate: a viable source of stem cells for bone regeneration. A systematic review
DOI:
https://doi.org/10.33448/rsd-v10i11.19265Keywords:
Bone marrow; Bone regeneration; Bone; Systematic review; Stem cells.Abstract
This systematic review evaluated the effectiveness of bone marrow aspirate (BMA) to enhance bone repair in humans. Comprehensive survey of ramdomized clinical trials published up to June 2021 and listed in PubMed/MEDLINE, EMBASE, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers independently searched eligible studies, made a final article selection, and extracted the data of the selected studies to evaluate it qualitatively. Overall, 13 studies were included in the review. Experimental models involved Posttraumatical aseptic nonunions of long bones of the upper limb, alveolar ridges following tooth extraction, atrophic mandibular fracture, benign bone lesions, bilateral tibial lengthening, fracture of intracapsular neck femur, maxillary horizontal ridge augmentation, non-traumatic femoral head necrosis, and sinus maxillary augmentation. The analyses included radiography, tomography, biopsies, and clinical evaluations. Ten studies reported enahanced bone formation (primary outcome) with combined use or not of BMA with other biomaterials and three studies found no benefit resulting from the use of BMA to treat bony defects. Secundary outcomes related to the healing process were also evaluated and positive, such as postoperative complications and pain visual analogue score. Within the limits of the present study, it can be concluded that BMA can improve the early stages of bone healing process.
References
Badiavas, E. V., & Falanga. V. (2013). Treatment of chronic wounds with bone marrow-derived cells. Arch. Dermatol. 139: 510-516.
Bansal, S., Chauhan, V., Sharma, S., Maheshwari, R., Juyal, A., & Raghuvanshi, S. (2009). Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute for posterolateral spinal fusion. Indian J. Orthop. 43: 234-239.
Bara, J. J., Richards, R. G., Alini, M., & Stoddart, M. J. (2014). Concise review: bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic. Stem Cells. 32: 1713-1723.
Burastero, G., Scarfì, S., Ferraris, C., Fresia, C., Sessarego, N., Fruscione, F., Monetti, F., Scarfò, F., Schupbach, P., Podestà, M., Grappiolo, G., & Zocchi, E. (2010). The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats. Bone. 47: 117-126.
Clines, G. A. (2010). Prospects for Osteoprogenitor Stem Cells in Fracture Repair and Osteoporosis. Curr. Opin. Organ. Transpl. 15: 73-78.
Clough, B. H., McCarley, M. R., Krause, U., Zeitouni, S., Froese, J. J., McNeill, E. P., Chaput, C. D., Sampson, H. W., & Gregory, C. A. (2015). Bone regeneration with osteogenically enhanced mesenchymal stem cells and their extracellular matrix proteins. J. Bone Miner. Res. 30: 83-94.
Da Costa, C. E. S., Pelegrine, A. A., Fagundes, D. J., Simoes, M. de J., & Taha, M. O. (2011). Use of corticocancellous allogeneic bone blocks impregnated with bone marrow aspirate: A clinical, tomographic, and histomorphometric study. Gen. Dent. 59: e200-e205.
Damron, T. A., Lisle, J., Craig, T., Wade, M., Silbert, W., & Cohen, H. (2013). Ultraporous B-tricalcium phosphate alone or combined with bone marrow aspirate for benign cavitary lesions. J Bone Joint Surg Am. 95: 158-166.
Duque, G. (2008). Bone and fat connection in aging bone. Curr. Opin. Rheumatol. 20: 429-434.
El-Adl, G., & Ali, A. M. (2013). Does bone marrow affect the radiological outcome when added to biphasic ceramic graft in treatment of benign bone lesions?. Eur. J. Orthop. Surg. Traumatol. 23: 13-20.
Fontes Martins, L. C., Sousa Campos de Oliveira, A. L., Aloise, A. C., Scavone de Macedo, L. G., Teixeira, M. L., Moy, P. K., & Pelegrine, A. A. (2021). Bone marrow aspirate concentrate and platelet-rich fibrin in fresh extraction sockets: A histomorphometric and immunohistochemical study in humans. J. Craniomaxillofac. Surg. 49: 104–109.
Gao, C., Gao, Q., Li, Y., Rahaman, M.N., Teramoto, A., & Abe, K. (2012). Preparation and in vitro characterization of electrospun PVA scaffolds coated with bioactive glass for bone regeneration. J. Biomed. Mater. Res. Part A. 100: 1324-1334.
Greenberger, J. S., & Epperly, M. (2009). Bone Marrow-Derived Stem Cells and Radiation Response. Semin. Radiat. Oncol. 19: 133-139.
Gupta, G. J., Karki, K., Jain, P., & Saxena, A. K. (2017). Autologous Bone Marrow Aspirate Therapy for Skin Tissue Engineering and Tissue Regeneration. Adv. Wound Care. 6: 135-142.
Harada, N., Watanabe, Y., Sato, K., Abe, S., Yamanaka, K., Sakai, Y., Kaneko, T., & Matsushita, T. (2014). Bone regeneration in a massive rat femur defect through endochondral ossification achieved with chondrogenically differentiated MSCs in a degradable scaffold. Biomaterials. 35: 7800-7810.
He, N., Zhang, L., Cui, J., & Li, Z. (2014). Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells. Bone Marrow Res. 2014: 128436.
Isern, J., & Méndez-Ferrer, S. (2011). Stem cell interactions in a bone marrow niche. Current. Osteoporos. Rep. 9: 210-218.
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J., Gavaghan, D. J., & McQuay, H. J. (1996). Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control. Clin. Trials. 17: 1-12.
Jäger, M., Herten, M., Fochtmann, U., Fischer, J., Hernigou, P., Zilkens, C., Hendrich, C., & Krauspe, R. (2011). Bridging the gap: Bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J. Orthop. Res. 29: 173-180.
Kaigler, D., Pagni, G., Park, C.H., Tarle, S.A., Bartel, R.L., Giannobile, W.V. (2010). Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration. Tissue Eng. Part A. 16: 2809- 2820.
Kraus, K. H., & Kirker-Head, C. (2006). Mesenchymal stem cells and bone regeneration. Vet. Surg. 35: 232-242.
Lana, J. F., da Fonseca, L. F., Azzini, G., Santos, G., Braga, M., Cardoso Junior, A. M., Murrell, W. D., Gobbi, A., Purita, J., & Percope de Andrade, M. A. (2021). Bone Marrow Aspirate Matrix: A Convenient Ally in Regenerative Medicine. Int. J. Mol. Sci. 22: 2762.
Landis, J. R., & Koch, G. G. (1977). The Measurement of Observer Agreement for Categorical Data. Biometrics. 33: 159-174.
Lee, D. H., Ryu, K. J., Kim, J. W., Kang, K. C., & Choi, Y. R. (2014). Bone Marrow Aspirate Concentrate and Platelet-rich Plasma Enhanced Bone Healing in Distraction Osteogenesis of the Tibia. Clin. Orthop. Rel. Res. 472: 3789-3797.
Lemos, C. A. A., Mello, C. C., dos Santos, D. M., Verri, F. R., Goiato, M. C., & Pellizzer, E. P. (2016). Effects of platelet-rich plasma in association with bone grafts in maxillary sinus augmentation: a systematic review and meta-analysis. Int. J. Oral Maxillofac. Surg. 45: 517-525.
Mannelli, G., Arcuri, F., Conti, M., Agostini, T., Raffaini, M., & Spinelli, G. (2017). The role of bone marrow aspirate cells in the management of atrophic mandibular fractures by mini-invasive surgical approach: Single-institution experience. J. Cranio-Maxillofacial Surg. 45: 694-703.
Mazzotta, A., Stagni, C., Rocchi, M., Rani, N., Del Piccolo, N., Filardo, G., & Dallari, D. (2021). Bone marrow aspirate concentrate/platelet-rich fibrin augmentation accelerates healing of aseptic upper limb nonunions. J. Orthop. Traumatol. 22: 21.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & PRISMA Group. (2010). Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias. Int. J. Surg. 8: 336-341.
Nagata, M. J., Santinoni, C. S., Pola, N. M., de Campos, N., Messora, M. R., Bomfim, S. R., Ervolino, E., Fucini, S. E., Faleiros, P. L., Garcia, V. G., Bosco, A. F. (2013). Bone marrow aspirate combined with low-level laser therapy: A new therapeutic approach to enhance bone healing. J. Photochem. Photobiol. B Biol. 121: 6-14.
Oliveira, H. F. E., Verri, F., Lemos, C. A., Cruz, R., Batista, V. E. S., Pellizzer, E., Santinoni, C. (2020). Clinical Evidence for Treatment of Class II Periodontal Furcation Defects. Systematic Review and Meta-analysis. J. Int. Acad. Periodontol. 22:117-128.
Pasquali, P. J., Teixeira, M. L., de Oliveira, T. A., de Macedo, L. G., Aloise, A. C., Pelegrine, A. A. (2015). Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate: A Histomorphometric Study in Humans. Int. J. Biomater. 2015: 121286.
Pelegrine, A. A., da Costa, C. E., Correa, M. E., Marquesm J. F. Jr. (2010). Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft. Clin. Oral Implants. Res. 21: 535-542.
Pelegrine, A. A., Teixeira, M. L., Sperandio, M., Almada, T. S., Kahnberg, K. E., Pasquali, P. J., Aloise, A. C. (2016). Can bone marrow aspirate concentrate change the mineralization pattern of the anterior maxilla treated with xenografts? A preliminary study. Contemp. Clin. Dent. 7: 21-26.
Pepke, W., Kasten, P., Beckmann, N.A., Janicki, P., Egermann, M. (2016). Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: A randomized prospective study. Orthop Rev. (Pavia). 8: 6162.
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., Marshak, D. R. (1999). Multilineage Potential of Adult Human Mesenchymal Stem Cells. Science. 284: 143-147.
Salamanna, F., Contartese, D., Nicoli Aldini, N., Barbanti Brodano, G., Griffoni, C., Gasbarrini, A., Fini, M. (2018). Bone marrow aspirate clot: A technical complication or a smart approach for musculoskeletal tissue regeneration? J. Cell Physiol. 233: 2723-2732.
Santinoni, C. D., Oliveira, H. F., Batista, V. E., Lemos, C. A., Verri, F. R. (2017). Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review. J. Photochem. Photobiol. B Biol. 169: 83-89.
Santinoni, C. S., Neves, A. P. C., Almeida, B. F. M., Kajimoto, N. C., Pola, N. M., Caliente, E. A., Belem, E. L. G., Lelis, J. B., Fucini, S. E., Messora, M. R., Garcia, V. G., Bomfim, S. R. M., Ervolino, E., Nagata, M. J. H. (2021). Bone marrow coagulated and low-level laser therapy accelerate bone healing by enhancing angiogenesis, cell proliferation, osteoblast differentiation, and mineralization. J. Biomed. Mater. Res. A. 109: 849-858.
Sauerbier, S., Rickert, D., Gutwald, R., Nagursky, H., Oshima, T., Xavier, S. P., Christmann, J., Kurz, P., Menne, D., Vissink, A., Raghoebar, G., Schmelzeisen, R., Wagner, W., Koch, F. P. (2011). Bone Marrow Concentrate and Bovine Bone Mineral for Sinus Floor Augmentation: A Controlled, Randomized, Single-Blinded Clinical and Histological Trial—Per-Protocol Analysis. Tissue Eng. Part A. 17: 2187-2197.
Schneider, R. K., Puellen, A., Kramann, R., Raupach, K., Bornemann, J., Knuechel, R., Pérez-Bouza, A., Neuss, S. (2010). The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds. Biomaterials. 31: 467-480.
Siegel, H. J., Baird, R. C. 3rd, Hall, J., Lopez-Ben, R., Lander, P. H. (2008). The outcome of composite bone graft substitute used to treat cavitary bone defects. Orthopedics. 31: 754.
Smiler, D., Soltan, M., Albitar, M. (2008). Toward the Identification of Mesenchymal Stem Cells in Bone Marrow and Peripheral Blood for Bone Regeneration. Implant Dent. 17: 236-274.
Soltan, M., Smiler, D., Prasad, H. S., Rohrer, M. D. (2017). Bone Block Allograft Impregnated with Bone Marrow Aspirate. Implant Dent. 16: 329- 339.
Tewari, D., Khan, M. P., Sagar, N., China, S. P., Singh, A. K., Kheruka, S. C., Barai, S., Tewari, M. C., Nagar, G. K., Vishwakarma, A. L., Ogechukwu, O. E., Bellare, J. R., Gambhir, S., Chattopadhyay, N. (2015). Ovariectomized Rats with Established Osteopenia have Diminished Mesenchymal Stem Cells in the Bone Marrow and Impaired Homing, Osteoinduction and Bone Regeneration at the Fracture Site. Stem Cell Rev. Reports. 11: 309-321.
U, V., Mehrotra, D., Howlader, D., Kumar, S., Anand, V. (2019). Bone Marrow Aspirate in Cystic Maxillofacial Bony Defects. J. Craniofac. Surg. 30: e247-e251.
Verma, N., Singh, M. P., Ul-Haq, R., Rajnish, R. K., Anshuman, R. (2017). Outcome of bone marrow instillation at fracture site in intracapsular fracture of femoral neck treated by head preserving surgery. Chinese J. Traumatol. 20: 222-225.
Weel, H., Mallee, W. H., Van Dijk, C. N., Blankevoort, L., Goedegebuure, S., Goslings, J. C., Kennedy, J. G., Kerkhoffs, G. M. (2015). The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures, a double-blind randomized controlled trial. BMC Musculoskelet. Disord. 16: 211.
Zhang, Z. Y., Teoh, S. H., Chong, M. S., Schantz, J. T., Fisk, N. M., Choolani, M. A., & Chan, J. (2009). Superior Osteogenic Capacity for Bone Tissue Engineering of Fetal Compared with Perinatal and Adult Mesenchymal Stem Cells. Stem Cells. 27: 126-137.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Carolina dos Santos Santinoni; Yara Loyanne de Almeida Silva Levi; João Paulo Pelágio Toneto; João Augusto Cazuza; Luciana Prado Maia; Fellippo Ramos Verri
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.