Download PDF
CC BY 4.0 · VCOT Open 2020; 03(01): e1-e10
DOI: 10.1055/s-0040-1701470
Clinical Communication
Georg Thieme Verlag KG Stuttgart · New York

Treatment of Monolateral Legg-Calvé-Perthes Disease with Autologous Bone Marrow Mononuclear Cells in 32 Dogs

Alberto Maria Crovace
1   IRCSS Saverio De Bellis, Castellana Grotte (Bari), Italy
,
Luca Lacitignola 
2   Dipartimento dell'Emergenze e trapianti di Organo, Università degli Studi di Bari, sez Cliniche veterinarie e p.a., Bari, Puglia, Italy
,
Francesco Staffieri
2   Dipartimento dell'Emergenze e trapianti di Organo, Università degli Studi di Bari, sez Cliniche veterinarie e p.a., Bari, Puglia, Italy
,
Edda Francioso
2   Dipartimento dell'Emergenze e trapianti di Organo, Università degli Studi di Bari, sez Cliniche veterinarie e p.a., Bari, Puglia, Italy
,
Giacomo Rossi
3   University of Camerino School of Bioscience and Veterinary Medicine, Camerino, Marche, Italy
,
Antonio Crovace
2   Dipartimento dell'Emergenze e trapianti di Organo, Università degli Studi di Bari, sez Cliniche veterinarie e p.a., Bari, Puglia, Italy
› Author Affiliations
Further Information

Publication History

02 July 2019

04 December 2019

Publication Date:
28 February 2020 (online)

   Permissions and Reprints

Abstract

Objective In the present study, we report our results of the use of autologous bone marrow mononuclear cells (BMMCs) as a minimally invasive treatment for Legg-Calvé-Perthes in dogs.

Study Design In accordance with Ljunggren's scale, inclusion criteria were determined by clinical condition and radiographic features of the disease, resulting in 32 dogs enrolled in this retrospective study from 2007 to 2019. Bone marrow was collected from each dog from the iliac crest and the mononuclear fraction was separated with density gradient centrifugation. The mean number of BMMCs was 104.7 ± 46.5 × 106 cells. The mean BMMC colony-forming units were 71.6 ± 51.9 × 102/mL.

Cells were suspended in fibrin glue before BMMC administration and implanted via transcutaneous injection under computed tomography or radiographic guidance, using a Jamshidi needle inserted through the femoral head and neck.

Results A progressive reduction of pain within 3 weeks after BMMC administration was observed in 28 patients, with gradually increased weight bearing on the affected limb. In four dogs, however, pain and lameness persisted and at 3 months post-BMMC injection, femoral head and neck resection was performed. Histological and immunohistochemical studies were done on samples from those four dogs, which showed evidence of formation of new cartilage and subchondral bone in the area where cells were implanted.

Clinical Significance Based on these results, BMMC therapy may be considered as effective and minimally invasive treatment option for LCPD in dogs.

Keywords

Legg-Calvé-Perthes disease - dog - bone marrow mononuclear cells - femoral head
 

  • References

  • 1 Calvé J. On a particular form of pseudo-coxalgia associated with a characteristic deformity of the upper end of the femur. 1910. Clin Orthop Relat Res 2006; 451 (451) 14-16
    CrossrefPubMedGoogle Scholar
  • 2 Legg AT. An obscure affection of the hip joint. 1910. Clin Orthop Relat Res 2006; 451 (451) 11-13
    CrossrefPubMedGoogle Scholar
  • 3 Perthes G. The classic: on juvenile arthritis deformans. 1910. Clin Orthop Relat Res 2012; 470 (09) 2349-2368
    CrossrefPubMedGoogle Scholar
  • 4 Tutt J. Tuberculosis of the hip joint in a cairn terrier. Vet Rec 1935; (47) 428-431
    PubMedGoogle Scholar
  • 5 Nunamaker DM. Legg-Calvé-Perthes disease. In: Newton CD, Nunamaker DM. , eds. Textbook of Small Animal Orthopaedics. Chapter 82. Philadelphia: Lippincott; 1985: 949-952
    Google Scholar
  • 6 Roperto F, Papparella S, Crovace A. Legg-Calvé-Perthes disease in dogs - histological and ultrastructural investigations. J Am Anim Hosp Assoc 1992; 28: 156-162
    PubMedGoogle Scholar
  • 7 Lee R, Fry PD. Some observations on the occurrence of Legg-Calvé-Perthes' disease (coxaplana) in the dog, and an evaluation of excision arthroplasty as a method of treatment. J Small Anim Pract 1969; 10 (05) 309-317
    CrossrefPubMedGoogle Scholar
  • 8 Ljunggren G. Legg-Perthes disease in the dog. Acta Orthop Scand 1967; (Suppl. 95) 95 , 1–79
    PubMedGoogle Scholar
  • 9 Gangji V, Hauzeur J-P, 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 (06) 1153-1160
    CrossrefPubMedGoogle Scholar
  • 10 Gangji V, Hauzeur J-P. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. Surgical technique. J Bone Joint Surg Am 2005; 87 (Pt 1, Suppl 1): 106-112
    CrossrefPubMedGoogle Scholar
  • 11 Kørbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept?. N Engl J Med 2003; 349 (06) 570-582
    CrossrefPubMedGoogle Scholar
  • 12 Cabrolier J, Molina M. [Is instillation of bone marrow stem cells at the time of core decompression useful for osteonecrosis of the femoral head?]. Medwave 2016; 16 (02) (Suppl. 01) e6406
    CrossrefPubMedGoogle Scholar
  • 13 Gao F, Sun W, Guo W, Wang B, Cheng L, Li Z. Combined with bone marrow-derived cells and rhBMP-2 for osteonecrosis after femoral neck fractures in children and adolescents: a case series. Sci Rep 2016; 6 (01) 30730
    CrossrefPubMedGoogle Scholar
  • 14 Liu Y, Liu S, Su X. Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg 2013; 133 (01) 125-133
    CrossrefPubMedGoogle Scholar
  • 15 Rackwitz L, Eden L, Reppenhagen S. , et al. Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head. Stem Cell Res Ther 2012; 3 (01) 7-15
    CrossrefPubMedGoogle Scholar
  • 16 Sun Y, Feng Y, Zhang C. The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Joint Bone Spine 2009; 76 (06) 685-690
    CrossrefPubMedGoogle Scholar
  • 17 Tabatabaee RM, Saberi S, Parvizi J, Mortazavi SM, Farzan M. Combining concentrated autologous bone marrow stem cells injection with core decompression improves outcome for patients with early-stage osteonecrosis of the femoral head: a comparative study. J Arthroplasty 2015; 30 (9, Suppl): 11-15
    CrossrefPubMedGoogle Scholar
  • 18 Wang B-L, Sun W, Shi Z-C. , et al. Treatment of nontraumatic osteonecrosis of the femoral head with the implantation of core decompression and concentrated autologous bone marrow containing mononuclear cells. Arch Orthop Trauma Surg 2010; 130 (07) 859-865
    CrossrefPubMedGoogle Scholar
  • 19 Jin H, Xia B, Yu N. , et al. The effects of autologous bone marrow mesenchymal stem cell arterial perfusion on vascular repair and angiogenesis in osteonecrosis of the femoral head in dogs. Int Orthop 2012; 36 (12) 2589-2596
    CrossrefPubMedGoogle Scholar
  • 20 Wang M, Liao Q, Zhou B, Qiu ZQ, Cheng LM. Preliminary study of influence of bone tissue from osteonecrosis of femoral head on the proliferation and differentiation of canine bone marrow mesenchymal stem cells [article in Chinese]. Zhonghua Yi Xue Za Zhi 2013; 93 (11) 856-859
    PubMedGoogle Scholar
  • 21 Crovace A, Favia A, Lacitignola L, Di Comite MS, Staffieri F, Francioso E. Use of autologous bone marrow mononuclear cells and cultured bone marrow stromal cells in dogs with orthopaedic lesions. Vet Res Commun 2008; 32 (Suppl. 01) S39-S44
    CrossrefPubMedGoogle Scholar
  • 22 Crovace A, Lacitignola L, Francioso E, Rossi G. Histology and immunohistochemistry study of ovine tendon grafted with cBMSCs and BMMNCs after collagenase-induced tendinitis. Vet Comp Orthop Traumatol 2008; 21 (04) 329-336
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Crovace A, Lacitignola L, Rossi G, Francioso E. Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon. Vet Med Int 2010; 2010: 250978
    PubMedGoogle Scholar
  • 24 Lacitignola L, Crovace A, Rossi G, Francioso E. Cell therapy for tendinitis, experimental and clinical report. Vet Res Commun 2008; 32 (Suppl. 01) S33-S38
    CrossrefPubMedGoogle Scholar
  • 25 Schmitz N, Laverty S, Kraus VB, Aigner T. Basic methods in histopathology of joint tissues. Osteoarthritis Cartilage 2010; 18 (Suppl. 03) S113-S116
    PubMedGoogle Scholar
  • 26 Busoni V, Rossi G, Denoix J-M. Arthrite septique du boulet: corrélation entre imagerie et examen anatomo-pathologique. Prat Vét Équine 1996; 28: 121-124
    PubMedGoogle Scholar
  • 27 McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis - shaping the immunological landscape. Nat Rev Rheumatol 2016; 12 (01) 63-68
    CrossrefPubMedGoogle Scholar
  • 28 Camplejohn KL, Allard SA. Limitations of safranin 'O' staining in proteoglycan-depleted cartilage demonstrated with monoclonal antibodies. Histochemistry 1988; 89 (02) 185-188
    CrossrefPubMedGoogle Scholar
  • 29 Amorin B, Alegretti AP, Valim V. , et al. Mesenchymal stem cell therapy and acute graft-versus-host disease: a review. Hum Cell 2014; 27 (04) 137-150
    CrossrefPubMedGoogle Scholar
  • 30 El-Jawhari JJ, El-Sherbiny YM, Jones EA, McGonagle D. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis. QJM 2014; 107 (07) 505-514
    CrossrefPubMedGoogle Scholar
  • 31 Wang D, Zhang H, Liang J. , et al. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant 2013; 22 (12) 2267-2277
    CrossrefPubMedGoogle Scholar
  • 32 Mattar P, Bieback K. Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol 2015; 6: 560-566
    PubMedGoogle Scholar
  • 33 Najar M, Raicevic G, Boufker HI. , et al. Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources. Cell Immunol 2010; 264 (02) 171-179
    CrossrefPubMedGoogle Scholar
  • 34 Sato K, Ozaki K, Oh I. , et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007; 109 (01) 228-234
    CrossrefPubMedGoogle Scholar
  • 35 Yoo KH, Jang IK, Lee MW. , et al. Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunol 2009; 259 (02) 150-156
    CrossrefPubMedGoogle Scholar
  • 36 Hernigou P, Guerin G, Homma Y. , et al. History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair?. Int Orthop 2018; 42 (07) 1739-1745
    CrossrefPubMedGoogle Scholar
  • 37 Hernigou P, Beaujean F, Lambotte JC. Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg Br 1999; 81 (02) 349-355
    CrossrefPubMedGoogle Scholar
  • 38 Hernigou P, Trousselier M, Roubineau F. , et al. Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress. Clin Orthop Surg 2016; 8 (01) 1-8
    PubMedGoogle Scholar
  • 39 Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001; 19 (03) 180-192
    CrossrefPubMedGoogle Scholar
  • 40 Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 49 (03) 507-521
    CrossrefPubMedGoogle Scholar
  • 41 Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 1966; 16 (03) 381-390
    PubMedGoogle Scholar
  • 42 Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 2013; 45 (11) e54
    CrossrefPubMedGoogle Scholar
  • 43 Hernigou P. Bone transplantation and tissue engineering, part IV. Mesenchymal stem cells: history in orthopedic surgery from Cohnheim and Goujon to the Nobel Prize of Yamanaka. Int Orthop 2015; 39 (04) 807-817
    CrossrefPubMedGoogle Scholar
  • 44 Jiang T, Xu G, Wang Q. , et al. In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects. Cell Death Dis 2017; 8 (06) e2851
    CrossrefPubMedGoogle Scholar
  • 45 Yan Z, Hang D, Guo C, Chen Z. Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. J Orthop Res 2009; 27 (04) 442-446
    CrossrefPubMedGoogle Scholar
  • 46 Hang D, Wang Q, Guo C, Chen Z, Yan Z. Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs. Cells Tissues Organs 2012; 195 (06) 495-506
    CrossrefPubMedGoogle Scholar
  • 47 Liu CH, Zhao DW, Wang BJ. Effects of different stress force stimulations on the expression of vascular endothelial growth factor in Beagle dogs in the repairing process of osteonecrosis of the femoral head [article in Chinese]. Zhonghua Yi Xue Za Zhi 2012; 92 (01) 40-44
    PubMedGoogle Scholar