Editorial- Regenerative medicine in Orthopaedics: Will the syringe replace the scalpel ?

Vol 35 | Issue 1 | Jan-April 2020 | page: 1-2 | Najmul Huda, Mir Shahidul Islam.


Authors: Najmul Huda, Mir Shahidul Islam  [1]

¹Department of Orthopaedic Surgery, Teerthankar Mahaveer Medical College, Moradabad, Uttarpradesh, India

Address of Correspondence:
Dr. Najmul Huda,
Teerthankar Mahaveer Medical College, Moradabad, Uttarpradesh, India
E-mail: editorjbjd1619@gmail.com


Undoubtedly the Orthopaedic field has seen enormous developments in the last few years. Inspite of state of the art instrumentation and cutting edge technology, there are certain musculoskeletal conditions, of diverse etiology, which are still not amenable to treatment. Of late there has been a substantial interest in the “biologic therapy” or so called regenerative medicine the potential ability of the stem cells to self renew and regenerate has opened up a plethora of avenues where they can be used.
Brittberg et al[1] was the first to introduce cell based therapy to Orthopaedics. They injected autologous chondrocytes in the cartilage defect of knee, which led to the formation of hyaline cartilage.
Stem cells are primitive cells that are capable of self renewal & differentiation into various tissue lines. They can be broadly classified as embryonic and adult stem cells. The embryonic stem cells (ESCs) are derived from the blastocysts whereas adult stem cells can be derived from tissues like the bone marrow, adipose tissue, skeletal muscles, dental pulp etc. Yamanaka et al in 2006, developed pluripotent stem cells from fibroblasts & called them induced pluripotent stem cells (iPScs)[2].
Though ESCs are far better but ethical concerns & their potential to from teratomas, preclude their use in clinical setting.
Mesenchymal stem cells (MSCs) are multipotent stem cells that were first identified by Friedenstein et al [3] and can be derived from bone marrow, muscle, adipose tissue, brain etc. It has now been established the cell yield is 500 times greater in adipose tissue than bone marrow. [4] The MSCs have been used in various musculoskeletal conditions like bone defects, non union, avascular necrosis, tendinopathies etc.
The management of large bone defects has traditionally been autologous/allogenic graft. Quarto et al [5] in 2001 used a hydroxyapatite scaffold loaded with MSCs which was implanted in the long bone defect. There was 100% integration of the scaffold to the parent bone. There have been many studies, which have shown the safety & efficacy of MSCs for managing bone defects.
Hernigou et al [6] was first to add Bone marrow aspirate concentrate (BMAC) to core decompression for osteonecrosis of the femoral head (ONFH). They reported good to excellent results. Sen et al [7] conducted a controlled trial on 51 osteonecrotic hips in 40 patients. 26 hips were treated with core decompression & autologous BMAC, whereas 25 hips underwent only core decompression. The follow up showed significant improvement in the clinical score and mean hip survival in the BMAC group. Recently many investigators have used MSCs isolated from the bone marrow aspirate for ONFH [8, 9, 10].
The use of MSc derived from bone marrow is now more or less an established from of treatment for Ficat state I & II of ONFH.
The use of MSC in bone healing has been studied extensively [11,12,13]. They have been used for non – unions, tibial osteotomies, distraction osteogenesis, spinal fusion & fractures.
Unlike bone, which has a great healing potential, articular cartilage has a limited regeneration potential. Any damage to AC eventually leads to osteoarthritis. Though most studies report encouraging results of MSC, injection into the knee joint. There are certain unanswered questions like the frequency & no. of injections, efficacy & safety of allogenic cells & efficacy in advanced O.A. There have been a few studies on the role of MSCs in tendon regeneration & tendinopathies. All these studies have reported positive results; however there is paucity of well – controlled studies.
Though extensive research in the field of stem cells has opened up many new avenues and raised hope of new treatment approaches, but at the same time there are many questions that need to be answered. The most important among them is the possibility of stem cell therapy & tumour formation. The probability of cultured cells undergoing mutations is another concern.
The role of stem cells in bone repair, tendon and cartilage regeneration is well established and here to stay. Diseases which are being managed surgically may be treated by simple injection of cells. A time may come when the syringe will replace the scalpel!!


References

1. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.N Engl J Med 1994; 331(14): 889-95.
2. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
3. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Mor -phol 1966; 16(3): 381-90.
4. Parker AM, Katz AJ. Adipose-derived stem cells for the regeneration of damaged tissues. Expert Opin Biol Ther 2006; 6:567–578.
5. Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344: 385-386.
6. Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405: 14-23.
7. Sen RK, Tripathy SK, Aggarwal S, Marwaha N, Sharma RR, Khandelwal N (2012) Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. J Arthroplasty 27: 679-686.
8. Aoyama T, Goto K, Kakinoki R, Ikeguchi R, Ueda M, Kasai Y, Maekawa T, Tada H, Teramukai S, Nakamura T, Toguchida J (2014) An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Tissue Eng Part B Rev 20: 233-242.
9. Kawate K, Yajima H, Ohgushi H, Kotobuki N, Sugimoto K, Ohmura T, Kobata Y, Shigematsu K, Kawamura K, Tamai K, Takakura Y (2006) Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. Artif Organs 30: 960-962.
10. Lim YW, Kim YS, Lee JW, Kwon SY (2013) Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med 45: e61. doi: 10.1038/emm.2013.128.
11. Connolly JF, Guse R, Tiedeman J, Dehne R (1991) Autologous marrow injection as a substitute for operative grafting of tibial nonunions. Clin Orthop Relat Res 266: 259-270.
12. Desai P, Hasan SM, Zambrana L, Hegde V, Saleh A, Cohn MR, Lane JM (2015) Bone Mesenchymal stem cells with growth factors successfully treat nonunions and delayed unions. HSS J 11: 104-111.
13. Dallari D, Savarino L, Stagni C, Cenni E, Cenacchi A, Fornasari P, Albisinni U, Rimondi E, Baldini N, Giunti A (2007) Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells. J Bone Joint Surg Am 89: 2413-2420.


How to Cite this Article: Huda N, Islam S M | Regenerative medicine in Orthopaedics: Will the syringe replace the scalpel? | Journal of Bone and Joint Diseases | Jan-April 2020; 35(1): 1-2.


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