Sains Malaysiana 50(6)(2021): 1727-1744

http://doi.org/10.17576/jsm-2021-5006-19

 

Assessing the Potential of Bone Marrow Concentrate for Cartilage Repair and Regeneration in Animal Models: A Systemic Review

(Menilai Potensi Kepekatan Sumsum Tulang untuk Pembaikan dan Pembaharuan Tulang Rawan dalam Model Haiwan: Suatu Kajian Sistemik)

 

NABILLAH ABD RADZAK, MALLIGA RAMAN MURALI* & TUNKU KAMARUL

 

Tissue Engineering Group, Department of Orthopaedic Surgery, NOCERAL, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

 

Diserahkan: 21 Februari 2020/Diterima: 8 Oktober 2020

 

ABSTRACT

Bone marrow concentrate (BMC) has been emerging as a promising regenerative source to accelerate cartilage regeneration in cartilage injuries and osteoarthritis. Though the number of stem cells in BMC is limited, BMC is rich in growth factors that promote stem cell differentiation and tissue regeneration. Despite of multiple reports available on the use of BMC for cartilage repair in humans and its use in clinical settings, only limited number of pre-clinical proof of concept studies have been reported in animal models. Hence, a systematic review focusing on the potential of BMC for the treatment of cartilage defect in animal models has been conducted. The systematic search of literature using three popular databases, ISI Web of Knowledge, PubMed and Scopus, were conducted without year restriction. Fifteen (n = 15) studies were found appropriate and included in this review. All of the included studies were of different animal models with cartilage defect. 13 out of 15 studies reported that the usage of BMC gave the best outcome compared to other treatment methods. Most of the findings provided good scoring on the tissue repair and the histological outcome. However, most of the BMC group outcomes did not give a significant difference when compared with other interventions such as the addition of platelet rich plasma, erythropoietin, hyaluronic acid, transforming growth factor, autologous tissue implant, genetic modification or scaffoldings. In conclusion, the published studies do suggest that BMC could provide a better cartilage repair. However, more preclinical studies are required to provide definitive conclusions.

 

Keywords: Animal study; bone marrow aspirate; bone marrow concentrate; cartilage; systematic review

 

ABSTRAK

Konsentrasi sumsum tulang (BMC) telah muncul sebagai sumber penjanaan semula yang berpotensi untuk mempercepatkan pertumbuhan tulang rawan dalam kecederaan rawan dan osteoartritis. Walaupun jumlah sel stem di BMC adalah terhad, BMC kaya dengan faktor pertumbuhan yang membantu dalam proses pembezaan sel stem dan penjanaan semula tisu. Walaupun terdapat banyak laporan mengenai penggunaan BMC untuk pembaikan tulang rawan pada manusia dan penggunaannya dalam tetapan klinikal, hanya sebilangan kecil bukti kajian konsep pra-klinikal yang terhad telah dilaporkan dalam model haiwan. Oleh itu, semakan sistematik yang menumpukan kepada potensi BMC untuk rawatan kecacatan tulang rawan dalam model haiwan telah dijalankan. Pencarian sastera sistematik menggunakan tiga pangkalan data popular, ISI Web of Knowledge, PubMed dan Scopus, telah dijalankan tanpa pembatasan tahun. Sebanyak lima belas (n = 15) kajian didapati bersesuaian dan disertakan dalam kajian ini. Semua kajian yang terpilih termasuk model haiwan yang berbeza dengan kecacatan tulang rawan. 13 daripada 15 kajian melaporkan bahawa penggunaan BMC memberi hasil yang terbaik berbanding kaedah rawatan lain. Kebanyakan penemuan memberikan skor yang baik ke atas pembaikan tisu dan hasil histologi. Walau bagaimanapun, kebanyakan hasil kumpulan BMC tidak memberikan perbezaan yang signifikan jika dibandingkan dengan campur tangan lain seperti penambahan platelet kaya plasma, eritropoietin, asid hialuronik, mengubah faktor pertumbuhan, implan tisu autologos, pengubahsuaian genetik atau perancah. Kesimpulannya, kajian yang diterbitkan menunjukkan bahawa BMC dapat memberikan pembaikan rawan yang lebih baik. Walau bagaimanapun, lebih banyak kajian pra-klinikal diperlukan untuk memberikan kesimpulan yang pasti.

 

Kata kunci: Haiwan; konsentrasi sumsum aspirat; konsentrasi sumsum tulang; rawan; semakan sistematik

 

RUJUKAN

Bekkers, J.E., Creemers, L.B., Tsuchida, A.I., van Rijen, M.H., Custers, R.J., Dhert, W.J. & Saris, D.B. 2013. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthritis Cartilage 21(7): 950-956.

Betsch, M., Thelen, S., Santak, L., Herten, M., Jungbluth, P., Miersch, D., Hakimi, M. & Wild, M. 2014. The role of erythropoietin and bone marrow concentrate in the treatment of osteochondral defects in mini pigs. PLoS ONE 9(3): e92766.

Betsch, M., Schneppendahl, J., Thuns, S., Herten, M., Sager, M., Jungbluth, P., Hakimi, M. & Wild, M. 2013. Bone marrow aspiration concentrate and platelet rich plasma for osteochondral repair in a porcine osteochondral defect model. PLoS ONE 8(8): e71602.

Chahla, J., Dean, C.S., Moatshe, G., Pascual-Garrido, C., Cruz, R.S. & LaPrade, R.F. 2016. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: A systematic review of outcomes. Orthopaedic Journal of Sports Medicine 4(1): 1-8.

Chu, C.R., Fortier, L.A., Williams, A., Payne, K.A., McCarrel, T.M., Bowers, M.E. & Jaramillo, D. 2018. Minimally manipulated bone marrow concentrate compared with microfracture treatment of full-thickness chondral defects a one-year study in an equine model. The Journal of Bone and Joint Surgery 100(2): 138-146.

Fortier, L.A., Potter, H.G., Rickey, E.J., Schnabel, L.V., Foo, L.F., Chong, L.R., Stokol, T., Cheetham, J. & Nixon, A.J. 2010. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. The Journal of Bone and Joint Surgery 92(10): 1927-1937.

Getgood, A., Henson, F., Skelton, C., Herrera, E., Brooks, R., Fortier, L.A. & Rushton, N. 2012. The augmentation of a collagen/glycosaminoglycan biphasic osteochondral scaffold with platelet-rich plasma and concentrated bone marrow aspirate for osteochondral defect repair in sheep: A pilot study. Cartilage 3(4): 351-363.

Hernigou, J., Vertongen, P., Chahidi, E., Kyriakidis, T., Dehoux, J.P., Crutzen, M., Boutry, S., Larbanoix, L., Houben, S., Gaspard, N., Koulalis D. & Rasschaert, J. 2018. International Orthopaedics 42(7): 1755-1767.

Huh, S.W., Shetty, A.A., Ahmad, S., Lee, D.H. & Kim, S.J. 2016. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC). Journal of Clinical Orthopaedics and Trauma 7(3): 153-156.

Ivkovic, A., Pascher, A., Hudetz, D., Maticic, D., Jelic, M., Dickinson, S., Loparic, M. & Pecina, M. 2010. Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Therapy 17(6): 779-789.

Jagodzinski, M., Liu, C., Guenther, D., Burssens, A., Petri, M., Abedian, R., Willbold, E., Krettek, C., Haasper, C. & Witte, F. 2013. Bone marrow-derived cell concentrates have limited effects on osteochondral reconstructions in the mini pig. Tissue Engineering: Part C Methods 20(3): 215-226.

Jin, L.H., Choi, B.H., Kim, Y.J., Park, S.R., Jin, C.Z. & Min, B.H. 2011. Implantation of bone marrow-derived buffy coat can supplement bone marrow stimulation for articular cartilage repair. Osteoarthritis and Cartilage 19(12): 1440-1448.

Madry, H., Gao, L., Eichler, H., Orth, P. & Cucchiarini, M. 2017. Bone marrow aspirate concentrate-enhanced marrow stimulation of chondral defects. Stem Cells International 2013: 1609685.

Murphy, M.B., Terrazas, J.A. & Buford, D.A. 2015. Bone marrow concentrate and platelet-rich plasma acquisition and preparation: Why technique matters. Technique in Regional Anaesthesia and Pain Management 19(1-2): 19-25.

Sampson, S., Bemden, A.B. & Aufiero, D. 2013. Autologous bone marrow concentrate: Review and application of a novel intra-articular orthobiologic for cartilage disease. The Physician and Sports Medicine 41(3): 7-18.

Saw, K.Y., Hussin, P., Loke, S.C., Azam, M., Chen, H.C., Tay, Y.G., Low, S., Wallin, K.L. & Ragavanaidu, K. 2009. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: An experimental study in a goat model. Arthroscopy: The Journal of Arthroscopic and Related Surgery 25(12): 1391-1400.

Veronesi, F., Desando, G., Fini, M., Parrilli, A., Lolli, R., Maglio, M., Martini, L., Giavaresi, G., Bartolotti, I., Grigolo, B. & Sartori, M. 2018. Bone marrow concentrate and expanded mesenchymal stromal cell surnatants as cell-free approaches for the treatment of osteochondral defects in a preclinical animal model. International Orthopaedics 43(1): 25-34.

Veronesi, F., Cadossi, M., Giavaresi, G., Martini, L., Setti, S., Buda, R., Giannini, S. & Fini, M. 2015. Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: An in vivo study. BMC Musculoskeletal Disorders 16: 233.

Yoon, D.S., Lee, K.M., Kim, S.H., Kim, S.H., Jung, Y., Kim, S.H., Park, K.H., Choi, Y., Ryu, H.A., Choi, W.J. & Lee, J.W. 2016. Synergistic action of IL-8 and bone marrow concentrate on cartilage regeneration through upregulation of chondrogenic transcription factors. Tissue Engineering Part A 22(3-4): 363-374.

Zhao, Q., Wang, S., Tian, J., Wang, L., Dong, S., Xia, T. & Wu, Z. 2013. Combination of bone marrow concentrate and PGA scaffolds enhance bone marrow stimulation in rabbit articular cartilage repair. Journal of Materials Science: Materials in Medicine 24(3): 793-801.

 

*Pengarang untuk surat-menyurat; email: drmurali@um.edu.my

 

 

     

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