Einsatz mesenchymaler Stammzellen beim Hund

Andrea Meyer-Lindenberg; Tim Kilchling

doi:10.1055/s-0038-1677407

Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere, Table of Contents

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018; 46(06): 416-425
DOI: 10.1055/s-0038-1677407

Für Studium und Praxis – For students and practitioners

Georg Thieme Verlag KG Stuttgart · New York

Einsatz mesenchymaler Stammzellen beim Hund

Use of mesenchymal stemcells in dogs

Andrea Meyer-Lindenberg

¹Chirurgische und Gynäkologische Kleintierklinik, Ludwig-Maximilians-Universität München

,

Tim Kilchling

¹Chirurgische und Gynäkologische Kleintierklinik, Ludwig-Maximilians-Universität München

› Author Affiliations

Abstract

Zusammenfassung

Mesenchymale Stammzellen (MSC) sind multipotente Zellen, die sich in verschiedene Zelltypen des Körpers differenzieren können, z. B. in osteogene, chondrogene, adipogene und myogene Richtungen. Die klinische Anwendung von Stammzellen stellt in der Humanmedizin ein seit Jahrzehnten etabliertes Verfahren dar. Auch in der Veterinärmedizin werden insbesondere beim Pferd schon seit längerem Therapien mit MSC durchgeführt. Seit ca. 15 Jahren findet dieses Verfahren auch beim Hund immer häufiger klinische Anwendung. Haupteinsatzgebiet sind hier Erkrankungen des Bewegungsapparats, vor allem Lahmheiten infolge osteoarthrotischer Veränderungen der großen Gelenke. Die Isolierung der MSC erfolgt in der Veterinärmedizin überwiegend aus dem Knochenmark oder dem Fettgewebe. Diese Arbeit gibt einen Überblick über Entnahmelokalisation, Gewinnung, Charakterisierung und Anwendungsmöglichkeiten von MSC in der Veterinärmedizin, insbesondere beim Hund. Dargestellt werden dabei die in der zugängli-chen Literatur beschriebenen Studien zur Therapie bei orthopädischen Erkrankungen des Hundes.

Summary

Mesenchymal stem cells (MSC) are multipotent cells, which are able to differentiate into various cell types of the body, as for example in osteogenic, chondrogenic, adipogenic and myogenic directions. In human medicine, the application of stem cells represents a well-established clinical procedure already applied for several decades. Addition-ally, in veterinary medicine, the stem-cell field is a rapidly growing sector for clinical use, particularly in horses. Recently, this treatment moda lity has also been commonly applied in dogs. The main field of application are diseases of the musculoskeletal system. Furthermore MSC are predominantly used for the treatment of lameness because of osteoarthritic changes of the large joints. In veterinary medicine, MSC are mainly isolated from bone marrow or adipose tissue. This artic le provides an overview of the removal site, isolation, characterisation and application of MSC. Moreover, studies available in the litera ture concerning the therapy of orthopaedic diseases in the dog using MSC are presented.

Schlüsselwörter

AD-MSC - BM-MSC - Osteoarthrose - Therapie

Key words

AD-MSC - BM-MSC - osteoarthritis - therapy

Full Text

References

Literatur
1 Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K. et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg 2003; 85-a: 1927-35.
2 Arnhold SJ, Goletz I, Klein H, Stumpf G, Beluche LA, Rohde C. et al. Isolation and characterization of bone marrow-derived equine mesenchymal stem cells. Am J Vet Res 2007; 68: 1095-105.
3 Astor DE, Hoelzler MG, Harman R, Bastian RP. Patient factors influencing the concentration of stromal vascular fraction (SVF) for adipose-derived stromal cell (ASC) therapy in dogs. Can J Vet Res 2013; 77: 177-82.
4 Baglioni S, Cantini G, Poli G, Francalanci M, Squecco R, Di Franco A. et al. Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell. PloS one. 2012; 7: e36569.
5 Bahamondes F, Flores E, Cattaneo G, Bruna F, Conget P. Omental adipose tissue is a more suitable source of canine mesenchymal stem cells. BMC Vet Res 2017; 13: 166.
6 Ball SG, Shuttleworth A, Kielty CM. Inhibition of platelet-derived growth factor receptor signaling regulates Oct4 and Nanog expression, cell shape, and mesenchymal stem cell potency. Stem Cells 2012; 30: 548-60.
7 Bearden RN, Huggins SS, Cummings KJ, Smith R, Gregory CA, Saunders WB. In-vitro characterization of canine multipotent stromal cells isolated from synovium, bone marrow, and adipose tissue: a donor-matched comparative study. Stem Cell Res Ther 2017; 8: 218.
8 Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R. et al. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther 2008; 9: 192-200.
9 Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S. et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 2007; 8: 272-84.
10 Burk J, Glauche SM, Brehm W, Crovace A, Francioso E, Hillmann A. et al. Characterisation and intracellular labelling of mesenchymal stromal cells derived from synovial fluid of horses and sheep. Vet J 2017; 222: 1-8.
11 Canapp Jr. SO, Leasure CS, Cox C, Ibrahim V, Carr BJ. Partial Cranial Cruciate Ligament Tears Treated with Stem Cell and Platelet-Rich Plasma Combination Therapy in 36 Dogs: A Retrospective Study. Frontiers in Veterinary Science 2016; 3: 112.
12 Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98: 1076-1084.
13 Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T. et al. Measurement of inclusive W and Z boson production cross sections in pp collisions at sqrt[s] = 8 TeV. Physical Review Letters 2014; 112: 191802.
14 Colleoni S, Bottani E, Tessaro I, Mari G, Merlo B, Romagnoli N. et al. Isolation, growth and differentiation of equine mesenchymal stem cells: effect of donor, source, amount of tissue and supplementation with basic fibroblast growth factor. Vet Res Commun 2009; 33: 811-821.
15 Csaki C, Matis U, Mobasheri A, Ye H, Shakibaei M. Chondrogenesis, osteo-genesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ultrastructural study. Histochem Cell Biol 2007; 128: 507-520.
16 Cuervo B, Rubio M, Sopena J, Dominguez JM, Vilar J, Morales M. et al. Hip osteoarthritis in dogs: a randomized study using mesenchymal stem cells from adipose tissue and plasma rich in growth factors. Int J Mol Sci 2014; 15: 13437-13460.
17 de Bakker E, Van Ryssen B, De Schauwer C, Meyer E. Canine mesenchymal stem cells: state of the art, perspectives as therapy for dogs and as a model for man. Vet Quart 2013; 33: 225-233.
18 De Schauwer C. Mesenchymal stem cells in daily veterinary practice: Are we there yet?. Vet J 2017; 225: 1-2.
19 Desantis S, Accogli G, Crovace A, Francioso EG, Crovace AM. Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells. Cytometry A 2018; 93: 73-81.
20 Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317.
21 Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD. et al. Clinical outcome after intra-articular administration of bone marrow derived mesenchymal stem cells in 33 horses with stifle injury. Vet Surg 2014; 43: 255-265.
22 Fortier LA, Nixon AJ, Williams J, Cable CS. Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells. Am J Vet Res 1998; 59: 1182-1187.
23 Fortier LA, Travis AJ. Stem cells in veterinary medicine. Stem Cell Res Ther 2011; 2: 9.
24 Fox SM. Painful decisions for senior pets. Vet Clin North Am Small Anim Pract 2012; 42: 727-748 vii.
25 Gingerich DA, Adams C, Gahring D, Aron D, Gaynor J, Black LL. et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 2007; 8 (04) 272-284.
26 Guercio A, Di Marco P, Casella S, Cannella V, Russotto L, Purpari G. et al. Production of canine mesenchymal stem cells from adipose tissue and their application in dogs with chronic osteoarthritis of the humeroradial joints. Cell Biol Int 2012; 36: 189-194.
27 Harman R, Carlson K, Gaynor J, Gustafson S, Dhupa S, Clement K. et al. A Prospective, Randomized, Masked, and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs. Frontiers in Veterinary Science. 2016; 3: 81.
28 Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep 2013; 15: 375.
29 Jackson WM, Lozito TP, Djouad F, Kuhn NZ, Nesti LJ, Tuan RS. Differentiation and regeneration potential of mesenchymal progenitor cells derived from traumatized muscle tissue. J Cell Mol Med 2011; 15: 2377-2388.
30 Jones EA, Crawford A, English A, Henshaw K, Mundy J, Corscadden D. et al. Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum 2008; 58: 1731-1740.
31 Joswig AJ, Mitchell A, Cummings KJ, Levine GJ, Gregory CA, Smith R. 3rd, et al. Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model. Stem Cell Res Ther 2017; 8: 42.
32 Jung DI, Ha J, Kang BT, Kim JW, Quan FS, Lee JH. et al. A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. J Neurol Sci 2009; 285: 67-77.
33 Kadiyala S, Young RG, Thiede MA, Bruder SP. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 1997; 6: 125-134.
34 Kamishina H, Deng J, Oji T, Cheeseman JA, Clemmons RM. Expression of neural markers on bone marrow-derived canine mesenchymal stem cells. Am J Vet Res 2006; 67: 1921-1928.
35 Kang BJ, Ryu HH, Park SS, Koyama Y, Kikuchi M, Woo HM. et al. Comparing the osteogenic potential of canine mesenchymal stem cells derived from adipose tissues, bone marrow, umbilical cord blood, and Wharton’s jelly for treating bone defects. J Vet Sci 2012; 13: 299-310.
36 Kazemi D, Shams Asenjan K, Dehdilani N, Parsa H. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017; 6: 98-107.
37 Kiefer KM, O‘Brien TD, Pluhar EG, Conzemius M. Canine adipose-derived stromal cell viability following exposure to synovial fluid from osteoarthritic joints. Vet Rec open 2015; 2: e000063.
38 Kisiday JD, Kopesky PW, Evans CH, Grodzinsky AJ, McIlwraith CW, Frisbie DD. Evaluation of adult equine bone marrow- and adipose-derived progenitor cell chondrogenesis in hydrogel cultures. J Orthop Res 2008; 26: 322-331.
39 Kisiel AH, McDuffee LA, Masaoud E, Bailey TR, Esparza Gonzalez BP, Nino-Fong R. Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum. Am J Vet Res 2012; 73: 1305-1317.
40 Koch TG, Heerkens T, Thomsen PD, Betts DH. Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol 2007; 7: 26.
41 Koch TG, Thomsen PD, Betts DH. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells. Cytotherapy. 2009; 11: 443-447.
42 Kraus KH, Kirker-Head C. Mesenchymal stem cells and bone regeneration. Vet Surg 2006; 35: 232-242.
43 Kriston-Pal E, Czibula A, Gyuris Z, Balka G, Seregi A, Sukosd F. et al. Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis. Can J Vet Res 2017; 81: 73-78.
44 Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2004; 103: 1669-1675.
45 Lin TM, Tsai JL, Lin SD, Lai CS, Chang CC. Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev 2005; 14: 92-102.
46 Linon E, Spreng D, Rytz U, Forterre S. Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs. Vet J 2014; 202: 448-454.
47 Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998; 176: 57-66.
48 Meyer-Lindenberg A, Kilchling T, Waselau AC, Consentino C, Alt C. Regenerative Medizin, Stammzellen/ACP: Was ist wirklich evidenzbasiert? 63. Jahrestagung der Deutschen Gesellschaft für Kleintiermedizin der Deutschen Veterinärmedizinischen Gesellschaft (DGK-DVG) vom 09–12. November 2017 in Berlin. Verlag DVG Service GmbH Gießen, 2017
49 Meyer-Lindenberg A, Layer A, Steigmeier-Raith S, Wergin M. Osteoarthrose – konservative Therapiemöglichkeiten inkl. Bestrahlung bei End-stage-Arthrosen. 62. Jahrestagung der Deutschen Gesellschaft für Klein-tiermedizin der Deutschen Veterinärmedizinischen Gesellschaft (DGKDVG) vom 27.–30. Oktober 2016 in Berlin. Verlag DVG Service GmbH Gießen, 2016
50 Muir P, Hans EC, Racette M, Volstad N, Sample SJ, Heaton C. et al. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture. PloS one. 2016; 11: e0159095.
51 Neupane M, Chang CC, Kiupel M, Yuzbasiyan-Gurkan V. Isolation and characterization of canine adipose-derived mesenchymal stem cells. Tissue Eng Part A 2008; 14: 1007-1015.
52 Nicolay NH, Perez RL, Saffrich R, Huber PE. Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic. Oncotarget 2015; 6 (23) 19366-19380.
53 Ock SA, Maeng GH, Lee YM, Kim TH, Kumar BM, Lee SL. et al. Donor-matched functional and molecular characterization of canine mesenchymal stem cells derived from different origins. Cell Transplant 2013; 22: 2311-2321.
54 Orbay H, Tobita M, Mizuno H. Mesenchymal stem cells isolated from adi-pose and other tissues: basic biological properties and clinical applications. Stem Cells International 2012; 2012: 461718.
55 Penny J, Harris P, Shakesheff KM, Mobasheri A. The biology of equine mesenchymal stem cells: phenotypic characterization, cell surface markers and multilineage differentiation. Front Biosci (Landmark Ed) 2012; 17: 892-908.
56 Reich CM, Raabe O, Wenisch S, Bridger PS, Kramer M, Arnhold S. Isolation, culture and chondrogenic differentiation of canine adipose tissue-and bone marrow-derived mesenchymal stem cells – a comparative study. Vet Res Commun 2012; 36: 139-148.
57 Requicha JF, Viegas CA, Albuquerque CM, Azevedo JM, Reis RL, Gomes ME. Effect of anatomical origin and cell passage number on the stemness and osteogenic differentiation potential of canine adipose-derived stem cells. Stem Cell Rev 2012; 8: 1211-1222.
58 Rodríguez-Jiménez FJ, Valdes-Sánchez T, Carrillo JM, Rubio M, MonleonPrades M, García-Cruz DM. et al. Platelet-rich plasma favors proliferation of canine adipose-derived mesenchymal stem cells in methacrylate-end-capped caprolactone porous scaffold niches. J Funct Biomater 2012; 3: 556-568.
59 Ryu HH, Lim JH, Byeon YE, Park JR, Seo MS, Lee YW. et al. Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J Vet Sci 2009; 10: 273-284.
60 Schroeck C, Eydt C, Geburek F, Kaiser L, Pabst F, Burk J. et al. Bone marrow-derived multipotent mesenchymal stromal cells from horses after euthanasia. Vet Med Sci 2017; 3: 239-251.
61 Screven R, Kenyon E, Myers MJ, Yancy HF, Skasko M, Boxer L. et al. Immunophenotype and gene expression profile of mesenchymal stem cells derived from canine adipose tissue and bone marrow. Vet Immunol Immunopathol 2014; 161: 21-31.
62 Smith RK, Garvican ER, Fortier LA. The current 舘state of play‘ of regenerative medicine in horses: what the horse can tell the human. Regen Med 2014; 9: 673-685.
63 Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev 2012; 21: 2724-2752.
64 Takemitsu H, Zhao D, Yamamoto I, Harada Y, Michishita M, Arai T. Comparison of bone marrow and adipose tissue-derived canine mesenchymal stem cells. BMC Vet Res 2012; 8: 150.
65 Taroni M, Cabon Q, Febre M, Cachon T, Saulnier N, Carozzo C. et al. Evaluation of the Effect of a Single Intra-articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells Compared to Oral Non-Steroidal Anti-inflammatory Treatment on the Postoperative Musculoskeletal Status and Gait of Dogs over a 6-Month Period after Tibial Plateau Leveling Osteotomy: A Pilot Study. Frontiers in Veterinary Science 2017; 4: 83.
66 Timmins NE, Kiel M, Gunther M, Heazlewood C, Doran MR, Brooke G. et al. Closed system isolation and scalable expansion of human placental mesenchymal stem cells. Biotechnol Bioeng 2012; 109: 1817-1826.
67 Van Velthoven CTJ, Kavelaars A, Heijnen CJ. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage. Pediatr Res 2012; 71: 474-481.
68 Vidal MA, Kilroy GE, Johnson JR, Lopez MJ, Moore RM, Gimble JM. Cell growth characteristics and differentiation frequency of adherent equine bone marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity. Vet Surg 2006; 35: 601-110.
69 Vidal MA, Robinson SO, Lopez MJ, Paulsen DB, Borkhsenious O, Johnson JR. et al. Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow. Vet Surg 2008; 37: 713-724.
70 Vieira NM, Brandalise V, Zucconi E, Secco M, Strauss BE, Zatz M. Isolation, characterization, and differentiation potential of canine adipose-derived stem cells. Cell Transplant 2010; 19: 279-289.
71 Vilar JM, Batista M, Morales M, Santana A, Cuervo B, Rubio M. et al. Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis. BMC Vet Res 2014; 10: 143.
72 Vilar JM, Cuervo B, Rubio M, Sopena J, Dominguez JM, Santana A. et al. Effect of intraarticular inoculation of mesenchymal stem cells in dogs with hip osteoarthritis by means of objective force platform gait analysis: concordance with numeric subjective scoring scales. BMC Vet Res 2016; 12: 223.
73 Vilar JM, Morales M, Santana A, Spinella G, Rubio M, Cuervo B. et al. Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Vet Res 2013; 9: 131.
74 Villatoro AJ, Fernandez V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed Res Int 2015; 2015: 527926.
75 Volk SW, Wang Y, Hankenson KD. Effects of donor characteristics and ex vivo expansion on canine mesenchymal stem cell properties: implications for MSC-based therapies. Cell Transplant 2012; 21: 2189-2200.
76 Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet (London, England). 2004; 363: 783-784.
77 Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ. et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004; 22: 1330-1337.
78 Wang W, Cao W. Treatment of osteoarthritis with mesenchymal stem cells. Sci China Life Sci 2014; 57: 586-595.
79 Webster RA, Blaber SP, Herbert BR, Wilkins MR, Vesey G. The role of mesenchymal stem cells in veterinary therapeutics – a review. New Zeal Vet J 2012; 60: 265-272.
80 Whitworth DJ, Banks TA. Stem cell therapies for treating osteoarthritis: prescient or premature?. Vet J 2014; 202: 416-424.
81 Wood JA, Chung DJ, Park SA, Zwingenberger AL, Reilly CM, Ly I. et al. Periocular and intra-articular injection of canine adipose-derived mesenchymal stem cells: an in vivo imaging and migration study. J Ocul Pharmacol Ther 2012; 28: 307-317.
82 Yaneselli KM, Kuhl CP, Terraciano PB, dos Santos de Oliveira F, Pizzato SB, Pazza K. et al. Comparison the characteristics of canine adipose tissue-derived mesenchymal stem cells extracted from different sites and at different passage numbers. J Vet Sci 2018; 19 (01) 13-20.
83 Yun S, Ku SK, Kwon YS. Adipose-derived mesenchymal stem cells and plate let-rich plasma synergistically ameliorate the surgical-induced osteoarthritis in Beagle dogs. J Orthop Surg Res 2016; 11: 9.
84 Zucconi E, Vieira NM, Bueno DF, Secco M, Jazedje T, Ambrosio CE. et al. Mesenchymal stem cells derived from canine umbilical cord vein – a novel source for cell therapy studies. Stem Cells Dev 2010; 19: 395-402.
85 Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001; 7: 211-228.