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Research Article

volume 54 issue 11 (november 2020) : 1422-1427,   Doi: 10.18805/ijar.B-3900

Clinical and Radiographic Effects of Bone Marrow Derived Mesenchymal Stem Cells Along with Local Insulin Therapy in Healing of Segmental Bone Defect in Diabetic Rabbits

S
Sonu Jaiswal
N
Narendra Singh Jadon
D
Deepti Bodh
R
R.K. Vishwakarma
1Department of Surgery and Radiology, College of Veterinary and Animal Sciences, Govind Ballabh Pant University of Agriculture andTechnology, Pantnagar-263 145, Uttarakhand, India.
Cite article:- Jaiswal Sonu, Jadon Singh Narendra, Bodh Deepti, Vishwakarma R.K. (2019). Clinical and Radiographic Effects of Bone Marrow Derived Mesenchymal Stem Cells Along with Local Insulin Therapy in Healing of Segmental Bone Defect in Diabetic Rabbits. Indian Journal of Animal Research. 54(11): 1422-1427. doi: 10.18805/ijar.B-3900.

ABSTRACT

The objective of present study was to investigate the efficacy of cultured allogenic bone marrow derived mesenchymal stem cell (BMMSCs) implant with insulin therapy for increasing osteosynthesis in bone gap defects in diabetic rabbits. Thirty six, clinically healthy New Zealand White rabbits were divided into four groups: A, B, C and D. Diabetes was induced experimentally in all rabbits, except group A. A 5 mm bone defect was created in right radii of all rabbits and following treatment was given: hydroxyapatite granules (group A and B), hydroxyapatite granules and insulin therapy (group C), cultured allogenic BMMSCs in hydroxyapatite scaffold and insulin therapy (group D). Clinical and radiographic parameters were recorded at days 0, 30, 60 and 90. It may be conducted that cultured allogenic bone marrow derived mesenchymal stem cells in hydroxyapatite scaffold along with local insulin therapy produces faster and better healing in alloxan-induced diabetic rabbits compared to healthy control, untreated diabetic and local insulin treated groups.

REFERENCES

  1. Arinzeh, T.L., Peter, S.J., Archambault, M.P., van den, B.C., Gordon, S., Kraus, K., Smith, A. and Kadivala, S. (2003). Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. Journal of Bone and Joint Surgery. 85: 1927-1935. 
  2. Boquist, L., Nelson, L. and Lorentzon, R. (1983). Uptake of labeled alloxan in mouse organs and mitochandria in vivo and in vitro. Endocrinoogy. 113: 943-948.
  3. Borena, B.M., Pawde, A.M., Amarpal, Aithal, H. P., Kinjavdekar, P, Singh, R. and Kumar, D. (2009) Autologous bone marrow-derived cells for healing of excisional dermal wounds of rabbits. Veterinary Record. 165: 563-568.
  4. Bruder, S.P., Kraus, K.H., Goldberg, V.M. and Kadiyala, S. (1998). The effect of implants loaded with autologous MSCs on the healing of canine segmental bone defects. Journal of Bone and Joint Surgery. 80: 985-996.
  5. Chang, S., Hypolite, J.A., Changolkar, A., Wein, A.J., Chacko, S. and Di Santo, M. E. (2003). Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase-â. International Journal of Impotence Research. 15: 53-62.
  6. Ferron, M., Wei, J., Yoshizawa, T., Del, Fattore, A., DePinho, R. A., Teti, A. and Ducy, P. (2010). Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 142: 296-308.
  7. Gandhi, A., Doumas, C., O’Connor J. P., Parsons, J. R. and Lin, S.S. (2006). The effects of local platelet rich plasma delivery on diabetic fracture healing. Bone. 38: 540-546. 
  8. Haldeman, S., Carroll, L., Cassidy, J.D., Schubert, J. and Nygren, A. (2008). The bone and joint decade 2000–2010 task force on neck pain and its associated disorders. Spine. 33: 5-7. 
  9. Krampera, M., Pizzolo, G., Aprili, G. and Franchini M. (2006). Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 39: 678-683.
  10. Lee, L.Y., Choi, M. H., Shin, E. Y. and Kang, Y.K. (2010). Autologous MSCs loaded in Gelfoam for structural bone allograft healing in rabbits. Cell Tissue Bank. 16: 144-150. 
  11. Lieberman, J.R.., Daluiski A. and Einhorn, T. A. (2002). The role of growth factors in the repair of bone: Biology and clinical applications. Journal of Bone and Joint Surgery. American.. 84-A: 1032-1044.
  12. Ozkan, K., Eralp, L., Kocaglu, M., Ahishali, B., Bilgic, B., Mitlu, Z., Turker, M., Ozkan, F.U., Sahin, K. and Guven, M. (2007). The effect of TGFâ-1 on the regenerate bone in distraction osteogenesis. Growth Factors. 25: 101-107.
  13. Paglia, D. N., Mason, K., Breitbart, E. A., Vaidya, S., Graves, D. T., O’Connor, J. P. and Lin, S. S. 2011. Effects of diabetes on bone homeostasis, regeneration and the role of insulin in bone. US Musculoskeletal Review. 6: 50-55.
  14. Park, J.S., Yang, H. N., Woo, D. G., Chung, H. M. and Park, K. H. (2009). In vitro and in vivo chondrogenesis of rabbit bone marrow–    derived stromal cells in fibrin matrix mixed with growth factor loaded in nanoparticles. Tissue Engineering. 15A (8): 2163-    2175.
  15. Pradhan, L., Nabzdyk, C. andersen, N. D., Lo Gerfo, F.W. and Veves, A. (2009). Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Reviews in Molecular Medicine. 11: e2.
  16. Quarto, R., Mastrogiacomo, M., Cancedda, R., Kutepov, S.M., Mukhachev, V., Lavroukov, A., Kon, E. and Marcacci, M. (2001). Repair of large bone defects with the use of autologous bone marrow stromal cells. New England Journal of Medicine. 344: 385-386.
  17. Reddy, G.K., Stehno-Bittel, L., Hamade, S. and Enwemeka, C. (2001).The biomechanical integrity of bone in experimental diabetes. Diabetes Research and Clinical Practice. 54:1-8.
  18. Retzepi, M. and Donos, N. (2010). The effect of diabetes mellitus on osseous healing. Clinical Oral Implants Research. 21: 673-681.
  19. Singh, J. (2009). Evaluation of osteogenic potential of autologous BMNCs with and without TGF-â1 or IGF-1 in rabbits. M. V. Sc. Thesis submitted to Indian Veterinary Research Institute (IVRI), Izatnagar.
  20. Snedecor, G.W. and Cochran, W. G. (1994). Statistical Methods. 8th ed, Lowa State University Press, Ames, pp. 217-235.
  21. Southwood, L.L, Frisbie, D. D., Kawcak, C. E. and Mcilwraith, C.W. (2005). Delivery of growth factors using gene therapy to enhance bone healing. Veterinary Surgery. 33: 565-578. 
  22. Volarevic, V., Arsenijevic, N., Lukic, M. and Stojkovic, M. (2011). Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells. 29: 5-10.
  23. Wang, J., Wan R, Mo, Y., Zhang, Q., Sherwood, L. C. and Chien, S. (2010). Creating a long-term diabetic rabbit model. Experimental Diabetes Research. 1-10.
  24. Zhou, G., Liu, W., Cui, L., Wang, X., Liu, T. and Cao, Y. (2006). Repair of porcine articular osteochondral defects in non-weight bearing areas with autologous bone marrow stromal cells. Tissue Engineering. 12: 3209-3221. 
  25. Zhou, J., Lin, H., Fang, T., Li, X., Dai, W., Uemura, T. and Dong, J. (2010). The repair of large segmental bone defect in rabbit with vascularized tissue engineered bone. Biomaterials. 31: 1171-1179.
  26. Zhu, W., Zhang, X., Wang, D., Lu ,W., Ou, Y., Han, Y., Zhou, K., Liu, H., Fen, W., Peng, L. C. and Zeng, H .Y. (2010). Experimental studies on the conduction function of nano-hydroxyapatite artificial bone. Micro and Nano Letters. 5: 19-27.
  27. Zou, X.H., Cai, H. X., Yin, Z., Chen, X., Jiang, Y., Z. and Hu H. (2009). A novel strategy incorporated the power of mesenchymal stem cells to allografts for segmental bone tissue engineering. Cell Transplant. 18: 433-441. 
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Indian Journal of Animal Research
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    Research Article

    volume 54 issue 11 (november 2020) : 1422-1427,   Doi: 10.18805/ijar.B-3900

    Clinical and Radiographic Effects of Bone Marrow Derived Mesenchymal Stem Cells Along with Local Insulin Therapy in Healing of Segmental Bone Defect in Diabetic Rabbits

    S
    Sonu Jaiswal
    N
    Narendra Singh Jadon
    D
    Deepti Bodh
    R
    R.K. Vishwakarma
    1Department of Surgery and Radiology, College of Veterinary and Animal Sciences, Govind Ballabh Pant University of Agriculture andTechnology, Pantnagar-263 145, Uttarakhand, India.
    Cite article:- Jaiswal Sonu, Jadon Singh Narendra, Bodh Deepti, Vishwakarma R.K. (2019). Clinical and Radiographic Effects of Bone Marrow Derived Mesenchymal Stem Cells Along with Local Insulin Therapy in Healing of Segmental Bone Defect in Diabetic Rabbits. Indian Journal of Animal Research. 54(11): 1422-1427. doi: 10.18805/ijar.B-3900.

    ABSTRACT

    The objective of present study was to investigate the efficacy of cultured allogenic bone marrow derived mesenchymal stem cell (BMMSCs) implant with insulin therapy for increasing osteosynthesis in bone gap defects in diabetic rabbits. Thirty six, clinically healthy New Zealand White rabbits were divided into four groups: A, B, C and D. Diabetes was induced experimentally in all rabbits, except group A. A 5 mm bone defect was created in right radii of all rabbits and following treatment was given: hydroxyapatite granules (group A and B), hydroxyapatite granules and insulin therapy (group C), cultured allogenic BMMSCs in hydroxyapatite scaffold and insulin therapy (group D). Clinical and radiographic parameters were recorded at days 0, 30, 60 and 90. It may be conducted that cultured allogenic bone marrow derived mesenchymal stem cells in hydroxyapatite scaffold along with local insulin therapy produces faster and better healing in alloxan-induced diabetic rabbits compared to healthy control, untreated diabetic and local insulin treated groups.

    REFERENCES

    1. Arinzeh, T.L., Peter, S.J., Archambault, M.P., van den, B.C., Gordon, S., Kraus, K., Smith, A. and Kadivala, S. (2003). Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. Journal of Bone and Joint Surgery. 85: 1927-1935. 
    2. Boquist, L., Nelson, L. and Lorentzon, R. (1983). Uptake of labeled alloxan in mouse organs and mitochandria in vivo and in vitro. Endocrinoogy. 113: 943-948.
    3. Borena, B.M., Pawde, A.M., Amarpal, Aithal, H. P., Kinjavdekar, P, Singh, R. and Kumar, D. (2009) Autologous bone marrow-derived cells for healing of excisional dermal wounds of rabbits. Veterinary Record. 165: 563-568.
    4. Bruder, S.P., Kraus, K.H., Goldberg, V.M. and Kadiyala, S. (1998). The effect of implants loaded with autologous MSCs on the healing of canine segmental bone defects. Journal of Bone and Joint Surgery. 80: 985-996.
    5. Chang, S., Hypolite, J.A., Changolkar, A., Wein, A.J., Chacko, S. and Di Santo, M. E. (2003). Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase-â. International Journal of Impotence Research. 15: 53-62.
    6. Ferron, M., Wei, J., Yoshizawa, T., Del, Fattore, A., DePinho, R. A., Teti, A. and Ducy, P. (2010). Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 142: 296-308.
    7. Gandhi, A., Doumas, C., O’Connor J. P., Parsons, J. R. and Lin, S.S. (2006). The effects of local platelet rich plasma delivery on diabetic fracture healing. Bone. 38: 540-546. 
    8. Haldeman, S., Carroll, L., Cassidy, J.D., Schubert, J. and Nygren, A. (2008). The bone and joint decade 2000–2010 task force on neck pain and its associated disorders. Spine. 33: 5-7. 
    9. Krampera, M., Pizzolo, G., Aprili, G. and Franchini M. (2006). Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 39: 678-683.
    10. Lee, L.Y., Choi, M. H., Shin, E. Y. and Kang, Y.K. (2010). Autologous MSCs loaded in Gelfoam for structural bone allograft healing in rabbits. Cell Tissue Bank. 16: 144-150. 
    11. Lieberman, J.R.., Daluiski A. and Einhorn, T. A. (2002). The role of growth factors in the repair of bone: Biology and clinical applications. Journal of Bone and Joint Surgery. American.. 84-A: 1032-1044.
    12. Ozkan, K., Eralp, L., Kocaglu, M., Ahishali, B., Bilgic, B., Mitlu, Z., Turker, M., Ozkan, F.U., Sahin, K. and Guven, M. (2007). The effect of TGFâ-1 on the regenerate bone in distraction osteogenesis. Growth Factors. 25: 101-107.
    13. Paglia, D. N., Mason, K., Breitbart, E. A., Vaidya, S., Graves, D. T., O’Connor, J. P. and Lin, S. S. 2011. Effects of diabetes on bone homeostasis, regeneration and the role of insulin in bone. US Musculoskeletal Review. 6: 50-55.
    14. Park, J.S., Yang, H. N., Woo, D. G., Chung, H. M. and Park, K. H. (2009). In vitro and in vivo chondrogenesis of rabbit bone marrow–    derived stromal cells in fibrin matrix mixed with growth factor loaded in nanoparticles. Tissue Engineering. 15A (8): 2163-    2175.
    15. Pradhan, L., Nabzdyk, C. andersen, N. D., Lo Gerfo, F.W. and Veves, A. (2009). Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Reviews in Molecular Medicine. 11: e2.
    16. Quarto, R., Mastrogiacomo, M., Cancedda, R., Kutepov, S.M., Mukhachev, V., Lavroukov, A., Kon, E. and Marcacci, M. (2001). Repair of large bone defects with the use of autologous bone marrow stromal cells. New England Journal of Medicine. 344: 385-386.
    17. Reddy, G.K., Stehno-Bittel, L., Hamade, S. and Enwemeka, C. (2001).The biomechanical integrity of bone in experimental diabetes. Diabetes Research and Clinical Practice. 54:1-8.
    18. Retzepi, M. and Donos, N. (2010). The effect of diabetes mellitus on osseous healing. Clinical Oral Implants Research. 21: 673-681.
    19. Singh, J. (2009). Evaluation of osteogenic potential of autologous BMNCs with and without TGF-â1 or IGF-1 in rabbits. M. V. Sc. Thesis submitted to Indian Veterinary Research Institute (IVRI), Izatnagar.
    20. Snedecor, G.W. and Cochran, W. G. (1994). Statistical Methods. 8th ed, Lowa State University Press, Ames, pp. 217-235.
    21. Southwood, L.L, Frisbie, D. D., Kawcak, C. E. and Mcilwraith, C.W. (2005). Delivery of growth factors using gene therapy to enhance bone healing. Veterinary Surgery. 33: 565-578. 
    22. Volarevic, V., Arsenijevic, N., Lukic, M. and Stojkovic, M. (2011). Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells. 29: 5-10.
    23. Wang, J., Wan R, Mo, Y., Zhang, Q., Sherwood, L. C. and Chien, S. (2010). Creating a long-term diabetic rabbit model. Experimental Diabetes Research. 1-10.
    24. Zhou, G., Liu, W., Cui, L., Wang, X., Liu, T. and Cao, Y. (2006). Repair of porcine articular osteochondral defects in non-weight bearing areas with autologous bone marrow stromal cells. Tissue Engineering. 12: 3209-3221. 
    25. Zhou, J., Lin, H., Fang, T., Li, X., Dai, W., Uemura, T. and Dong, J. (2010). The repair of large segmental bone defect in rabbit with vascularized tissue engineered bone. Biomaterials. 31: 1171-1179.
    26. Zhu, W., Zhang, X., Wang, D., Lu ,W., Ou, Y., Han, Y., Zhou, K., Liu, H., Fen, W., Peng, L. C. and Zeng, H .Y. (2010). Experimental studies on the conduction function of nano-hydroxyapatite artificial bone. Micro and Nano Letters. 5: 19-27.
    27. Zou, X.H., Cai, H. X., Yin, Z., Chen, X., Jiang, Y., Z. and Hu H. (2009). A novel strategy incorporated the power of mesenchymal stem cells to allografts for segmental bone tissue engineering. Cell Transplant. 18: 433-441. 
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