Eur J Pediatr Surg 2014; 24(03): 263-269
DOI: 10.1055/s-0034-1382777
Review
Georg Thieme Verlag KG Stuttgart · New York

Tissue Engineering Approaches in Skeletal Pediatric Disorders

Chiara Gentili
1   Department of Experimental Medicine (DIMES), University of Genoa, Laboratory of Regenerative Medicine, Genova, Italy
,
Michele Torre
2   Department of Pediatric Surgery, Istituto Giannina Gaslini, Genova, Italy
,
Ranieri Cancedda
1   Department of Experimental Medicine (DIMES), University of Genoa, Laboratory of Regenerative Medicine, Genova, Italy
› Author Affiliations
Further Information

Publication History

19 May 2014

22 May 2014

Publication Date:
22 June 2014 (online)

Abstract

The therapeutic use of stem cells is a very promising strategy in the area of regenerative medicine. The stem cell regenerative paradigm has been mostly based on the assumption that progenitor cells play a critical role in tissue repair by their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of affected cells at the site of injury. Preclinical and clinical skeletal studies, conducted in animal and adult series, support the use of mesenchymal stem cells (MSCs) for bone healing in critical clinical situations. These results have led to an increasing number of papers reporting the use of MSCs in adult clinical trials, whereas only few papers reported the use of these cells in pediatric skeletal disorders, probably because of unknown long-term results and long-life consequences of cellular therapy. The exponential growth of knowledge in adult MSCs could be translated and applied to pediatric disorders. Pediatric osteoarticular diseases have an enormous potential to be treated by MSCs, as severe congenital bone or local cartilage defects, not responding to conventional surgery treatment, might be successfully treated by cellular therapy. Translating basic stem cell research into routine therapies is a complex multistep process which entails the managing of the expected therapeutic benefits with the potential risks in correlation within the existing regulations. Here, we reported the state of art on the use of MSC in skeletal pediatric disorders.

 
  • References

  • 1 Bueno EM, Glowacki J. Cell-free and cell-based approaches for bone regeneration. Nat Rev Rheumatol 2009; 5 (12) 685-697
  • 2 Corselli M, Chen CW, Crisan M, Lazzari L, Péault B. Perivascular ancestors of adult multipotent stem cells. Arterioscler Thromb Vasc Biol 2010; 30 (6) 1104-1109
  • 3 Verfaillie CM. Adult stem cells: assessing the case for pluripotency. Trends Cell Biol 2002; 12 (11) 502-508
  • 4 Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med 2011; 6 (4) 481-492
  • 5 Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98 (5) 1076-1084
  • 6 Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003; 48 (12) 3464-3474
  • 7 Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis 2011; 14 (2) 211-215
  • 8 Horwitz EM. Marrow mesenchymal cell transplantation for genetic disorders of bone. Cytotherapy 2001; 3 (5) 399-401
  • 9 Le Blanc K, Götherström C, Ringdén O , et al. Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation 2005; 79 (11) 1607-1614
  • 10 Atala A. Tissue engineering of human bladder. Br Med Bull 2011; 97: 81-104
  • 11 Kim BS, Atala A, Yoo JJ. A collagen matrix derived from bladder can be used to engineer smooth muscle tissue. World J Urol 2008; 26 (4) 307-314
  • 12 Elliott MJ, De Coppi P, Speggiorin S , et al. Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study. Lancet 2012; 380 (9846) 994-1000
  • 13 Jorgensen C, Noël D. Mesenchymal stem cells in osteoarticular diseases. Regen Med 2011; 6 (6, Suppl): 44-51
  • 14 Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 1968; 2 (7583) 1366-1369
  • 15 Halme DG, Kessler DA. FDA regulation of stem-cell-based therapies. N Engl J Med 2006; 355 (16) 1730-1735
  • 16 Bollini S, Gentili C, Tasso R, Cancedda R. The regenerative role of the fetal and adult stem cell secretome. J Clin Med 2013; 2: 302-327
  • 17 Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004; 116 (6) 769-778
  • 18 da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells 2008; 26 (9) 2287-2299
  • 19 Kean TJ, Lin P, Caplan AI, Dennis JE. MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int 2013; 2013: 732742
  • 20 Mirabella T, Gentili C, Daga A, Cancedda R. Amniotic fluid stem cells in a bone microenvironment: driving host angiogenic response. Stem Cell Res (Amst) 2013; 11 (1) 540-551
  • 21 Otsuru S, Gordon PL, Shimono K , et al. Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms. Blood 2012; 120 (9) 1933-1941
  • 22 Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 2012; 20 (1) 14-20
  • 23 Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell 2011; 9 (1) 11-15
  • 24 Quarto R, Mastrogiacomo M, Cancedda R , et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 2001; 344 (5) 385-386
  • 25 Vacanti CA, Bonassar LJ, Vacanti MP, Shufflebarger J. Replacement of an avulsed phalanx with tissue-engineered bone. N Engl J Med 2001; 344 (20) 1511-1514
  • 26 Warnke PH, Wiltfang J, Springer I , et al. Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible. Biomaterials 2006; 27 (17) 3163-3167
  • 27 Bürger B, Beier R, Zimmermann M, Beck JD, Reiter A, Schrappe M. Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)—experiences from trial ALL-BFM 95. Pediatr Blood Cancer 2005; 44 (3) 220-225
  • 28 Kobayakawa M, Rydholm U, Wingstrand H, Pettersson H, Lidgren L. Femoral head necrosis in juvenile chronic arthritis. Acta Orthop Scand 1989; 60 (2) 164-169
  • 29 Strauss AJ, Su JT, Dalton VM, Gelber RD, Sallan SE, Silverman LB. Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol 2001; 19 (12) 3066-3072
  • 30 Castro Jr FP, Barrack RL. Core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis. Am J Orthop 2000; 29 (3) 187-194
  • 31 Beltran J, Knight CT, Zuelzer WA , et al. Core decompression for avascular necrosis of the femoral head: correlation between long-term results and preoperative MR staging. Radiology 1990; 175 (2) 533-536
  • 32 Low K, Mont MA, Hungerford DS. Steroid-associated osteonecrosis of the knee: a comprehensive review. Instr Course Lect 2001; 50: 489-493
  • 33 Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. J Bone Joint Surg Am 2004; 86-A (6) 1153-1160
  • 34 Müller I, Vaegler M, Holzwarth C , et al. Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis. Leukemia 2008; 22 (11) 2054-2061
  • 35 Kawamoto HJ. Craniofacial anomalies. Pediatric Surgery 2006; 787
  • 36 Weiss J, Kotelchuck M, Grosse SD , et al. Hospital use and associated costs of children aged zero-to-two years with craniofacial malformations in Massachusetts. Birth Defects Res A Clin Mol Teratol 2009; 85 (11) 925-934
  • 37 Chen TM, Wang HJ. Cranioplasty using allogeneic perforated demineralized bone matrix with autogenous bone paste. Ann Plast Surg 2002; 49 (3) 272-277 , discussion 277–279
  • 38 Turner CG, Klein JD, Gray FL, Ahmed A, Zurakowski D, Fauza DO. Craniofacial repair with fetal bone grafts engineered from amniotic mesenchymal stem cells. J Surg Res 2012; 178 (2) 785-790
  • 39 Behnia H, Khojasteh A, Soleimani M , et al. Secondary repair of alveolar clefts using human mesenchymal stem cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108 (2) e1-e6
  • 40 Levi B, Glotzbach JP, Wong VW , et al. Stem cells: update and impact on craniofacial surgery. J Craniofac Surg 2012; 23 (1) 319-322
  • 41 Pannier S. Congenital pseudarthrosis of the tibia. Orthop Traumatol Surg Res 2011; 97 (7) 750-761
  • 42 Mahnken AH, Staatz G, Hermanns B, Gunther RW, Weber M. Congenital pseudarthrosis of the tibia in pediatric patients: MR imaging. AJR Am J Roentgenol 2001; 177 (5) 1025-1029
  • 43 Ilizarov GA, Gracheva VI. Bloodless treatment of congenital pseudarthrosis of the crus with simultaneous elimination of shortening using dosed distraction [in Russian]. Ortop Travmatol Protez 1971; 32 (2) 42-46
  • 44 Paley D, Catagni M, Argnani F, Prevot J, Bell D, Armstrong P. Treatment of congenital pseudoarthrosis of the tibia using the Ilizarov technique. Clin Orthop Relat Res 1992; (280) 81-93
  • 45 Hernigou P, Beaujean F. Pseudarthrosis treated by percutaneous autologous bone marrow graft [in French]. Rev Chir Orthop Repar Appar Mot 1997; 83 (6) 495-504
  • 46 Garg NK, Gaur S. Percutaneous autogenous bone-marrow grafting in congenital tibial pseudarthrosis. J Bone Joint Surg Br 1995; 77 (5) 830-831
  • 47 Granchi D, Devescovi V, Baglìo SR , et al. Biological basis for the use of autologous bone marrow stromal cells in the treatment of congenital pseudarthrosis of the tibia. Bone 2010; 46 (3) 780-788
  • 48 Granchi D, Devescovi V, Baglio SR, Magnani M, Donzelli O, Baldini N. A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome. Cytotherapy 2012; 14 (3) 306-314
  • 49 Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP?. Implant Dent 2001; 10 (4) 225-228
  • 50 Mehrannia M, Vaezi M, Yousefshahi F, Rouhipour N. Platelet rich plasma for treatment of nonhealing diabetic foot ulcers: a case report. Can J Diabetes 2014; 38 (1) 5-8
  • 51 Sano H, Ichioka S, Minamimura A, Tanaka R, Ikebuchi K, Suzuki M. Treatment of chronic ulcer with elastic plasma protein and platelet film for wound dressing. J Plast Surg Hand Surg 2013; 47 (6) 462-466
  • 52 Wasterlain AS, Braun HJ, Harris AH, Kim HJ, Dragoo JL. The systemic effects of platelet-rich plasma injection. Am J Sports Med 2013; 41 (1) 186-193
  • 53 Moroz A, Deffune E. Platelet-rich plasma and chronic wounds: remaining fibronectin may influence matrix remodeling and regeneration success. Cytotherapy 2013; 15 (11) 1436-1439
  • 54 Zaky SH, Ottonello A, Strada P, Cancedda R, Mastrogiacomo M. Platelet lysate favours in vitro expansion of human bone marrow stromal cells for bone and cartilage engineering. J Tissue Eng Regen Med 2008; 2 (8) 472-481
  • 55 Xie X, Wang Y, Zhao C , et al. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 2012; 33 (29) 7008-7018
  • 56 Siclari A, Mascaro G, Gentili C, Cancedda R, Boux E. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clin Orthop Relat Res 2012; 470 (3) 910-919
  • 57 Pereira RC, Scaranari M, Benelli R , et al. Dual effect of platelet lysate on human articular cartilage: a maintenance of chondrogenic potential and a transient proinflammatory activity followed by an inflammation resolution. Tissue Eng Part A 2013; 19 (11-12) 1476-1488
  • 58 El Backly RM, Zaky SH, Muraglia A , et al. A platelet-rich plasma-based membrane as a periosteal substitute with enhanced osteogenic and angiogenic properties: a new concept for bone repair. Tissue Eng Part A 2013; 19 (1-2) 152-165
  • 59 Willing MC, Deschenes SP, Scott DA , et al. Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen. Am J Hum Genet 1994; 55 (4) 638-647
  • 60 Horwitz EM, Prockop DJ, Fitzpatrick LA , et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5 (3) 309-313
  • 61 Horwitz EM, Prockop DJ, Gordon PL , et al. Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 2001; 97 (5) 1227-1231
  • 62 Horwitz EM, Gordon PL, Koo WK , et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 2002; 99 (13) 8932-8937
  • 63 Klein JD, Turner CG, Ahmed A, Steigman SA, Zurakowski D, Fauza DO. Chest wall repair with engineered fetal bone grafts: an efficacy analysis in an autologous leporine model. J Pediatr Surg 2010; 45 (6) 1354-1360
  • 64 Steigman SA, Ahmed A, Shanti RM, Tuan RS, Valim C, Fauza DO. Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells. J Pediatr Surg 2009; 44 (6) 1120-1126 , discussion 1126
  • 65 Turner CG, Klein JD, Steigman SA , et al. Preclinical regulatory validation of an engineered diaphragmatic tendon made with amniotic mesenchymal stem cells. J Pediatr Surg 2011; 46 (1) 57-61