Improvement of Chronic Wound Healing by Pre-activated Bone Marrow Cells with Sodium Nitroprusside in Rabbits

Abstract

Aim of study This study investigated whether pre-activated bone marrow cells with sodium nitro prusside have effectiveness in the inhibition of diabetic wound healing in diabetic rabbits. In diabetic skin disorders and conditions involved redox state disturbances. The aim was to determine the effect of two minimum dosages of sodium nitro prusside, and its’ potential with bone marrow cells for chronic wound healing in-vivo.

Methods Full-thickness skin dorsal wounds were created on diabetic rabbits. The effects of two minimum concentrations of sodium nitro prusside solution with bone marrow cells on wound healing were studied. The useful combination of sodium nitro prusside with bone marrow cells on wound repair may be attributed to its functional influences on inflammation, angiogenesis, cell proliferation, matrix deposition, and remodeling.

Results The in-vivo experiments confirmed that pre-activated bone marrow cells contributed to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis. In histological results, improved collagen deposition, enhanced re-epithelization, angiogenesis, and decreased inflammatory infiltration were also detected in wound biopsies.

Conclusions For the treatment of chronic wounds, cell-based therapy was an attractive approach. Bone marrow cells have a low ability to differentiate various types of cells or late healing without pretreatment. So it was needed to increase their potency of differentiation. The transplantation of pretreated bone marrow cells with a prime quantity of sodium nitro prusside solution improved chronic wound healing with a greater level of growth factors and a minimum level of oxidative stress.

Key words

Sodium nitroprusside - Bone marrow cells - chronic wounds - Angiogenesis - Collagen

Publication History

Received: 08 June 2021
Received: 20 August 2021

Accepted: 22 August 2021

Article published online:
30 September 2021

• References

• 1 Icli B, Nabzdyk CS, Lujan-Hernandez J. et al. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a. J mol cell cardiol 2016; 91: 151-159
• 2 Pereira SG, Moura J, Carvalho E. et al. Microbiota of chronic diabetic wounds: ecology, impact, and potential for innovative treatment strategies. Frontiers in microbiology 2017; 8: 1791
• 3 Kandhwal M, Behl T, Kumar A. et al. Understanding the Potential Role and Delivery Approaches of Nitric Oxide in Chronic Wound Healing Management. Current Pharmaceutical Design. 2021; 27: 1999–2014
• 4 Bai Q, Han K, Dong K. et al. Potential Applications of Nanomaterials and Technology for Diabetic Wound Healing. International journal of nanomedicine 2020; 15: 9717
• 5 Sharifi S, Hajipour MJ, Gould L. et al. Nanomedicine in Healing Chronic Wounds: Opportunities and Challenges. Molecular Pharmaceutics 2021; 18: 550–575
• 6 Xu Z, Han S, Gu Z. et al. Advances and impact of antioxidant hydrogel in chronic wound healing. Advanced healthcare materials 2020; 9: 1901502
• 7 Zhao R, Jackson CJ, Xue M. Extracellular Matrix and Other Factors that Impact on Cutaneous Scarring. Chronic Wounds, Wound Dressings and Wound Healing: Springer; 2018. p. 135–178
• 8 Emre A, Bayram O, Salman B. et al. Sodium nitroprusside as a nitric oxide donor in a rat intestinal ischemiareperfusion model. Clinics 2008; 63: 91-96
• 9 Cherng YG, Chang HC, Lin YL. et al. Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-Mitochondria-Mediated caspase activation. Journal of orthopaedic research 2008; 26: 1018-1026
• 10 Wang R, Jiao H, Zhao J. et al. L-Arginine Enhances Protein Synthesis by Phosphorylating mTOR (Thr 2446) in a Nitric Oxide-Dependent Manner in C2C12 Cells. Oxidative medicine and cellular longevity. 2018; 2018
• 11 Colonna VDG, Bianchi M, Pascale V. et al. Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of nitric oxide synthase and a novel cardiovascular risk molecule. Medical science monitor 2009; 15: RA91-RA101
• 12 Wendehenne D, Pugin A, Klessig DF. et al. Nitric oxide: comparative synthesis and signaling in animal and plant cells. Trends in plant science 2001; 6: 177-183
• 13 Murohara T, Witzenbichler B, Spyridopoulos I. et al. Role of endothelial nitric oxide synthase in endothelial cell migration. Arteriosclerosis, thrombosis, and vascular biology 1999; 19: 1156-1161
• 14 Zhou X, Wang H, Zhang J. et al. Functional poly (ε-caprolactone)/chitosan dressings with nitric oxide-releasing property improve wound healing. Acta biomaterialia 2017; 54: 128-137
• 15 Moccia F, Negri S, Shekha M. et al. Endothelial Ca2+Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel. International journal of molecular sciences 2019; 20: 3962
• 16 Kwon DS, Gao X, Liu YB. et al. Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. International wound journal 2008; 5: 453-463
• 17 Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Current dermatology reports 2018; 7: 350-358
• 18 Balaji S, King A, Crombleholme TM. et al. The role of endothelial progenitor cells in postnatal vasculogenesis: implications for therapeutic neovascularization and wound healing. Advances in wound care 2013; 2: 283-295
• 19 Sahoo S, Dong F, DiVincenzo L. et al. Effect of Exosomes from Mesenchymal Stem Cells on Angiogenesis. Mesenchymal Stem Cell Derived Exosomes: The Potential for Translational Nanomedicine. 2015; doi:10.1016/B978-0-12-800164-6.00009-5
• 20 Shinagawa T, Takagi T, Tsukamoto D. et al. Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells. Cell stem cell 2014; 14: 217-227
• 21 Hu X, Wei L, Taylor TM. et al. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2. 1 channel and FAK activation. American journal of physiology-cell physiology 2011; 301: C362-C372
• 22 Baldari S, Di Rocco G, Piccoli M. et al. Challenges and strategies for improving the regenerative effects of mesenchymal stromal cell-based therapies. International journal of molecular sciences. 2017; 18: 2087
• 23 Griffin DR, Weaver WM, Scumpia PO. et al. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat mater 2015; 14: 737-744
• 24 Rodriguez-Menocal L, Shareef S, Salgado M. et al. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing. Stem cell res ther 2015; 6: 24
• 25 Kale S, Karihaloo A, Clark PR. et al. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. The journal of clinical investigation 2003; 112: 42-49
• 26 Fatima N, Saleem M. Transplantation of Bone Marrow Cells Preactivated With Sodium Nitroprusside Improves Acute Wound Healing in Rabbits. The International Journal of Lower Extremity Wounds. 2021: 15347346211029078
• 27 Sharma N, Mishra K, Ganju L. et al. Salidroside Exerts Anti-Inflammatory Effect by Reducing Nuclear Factor κB and Nitric Oxide Production in Macrophages. MOJ immunol 2018; 6: 00183
• 28 Wang Y-W, Wu Q, Chen G-Q. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 2004; 25: 669-675
• 29 Tong C, Hao H, Xia L. et al. Hypoxia pretreatment of bone marrow — derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia. Wound repair and regeneration 2016; 24: 45-56
• 30 Romana-Souza B, dos Santos JS, Bandeira LG. et al. Selective inhibition of COX-2 improves cutaneous wound healing of pressure ulcers in mice through reduction of iNOS expression. Life sciences 2016; 153: 82-92
• 31 Bao P, Kodra A, Tomic-Canic M. et al. The role of vascular endothelial growth factor in wound healing. Journal of surgical research 2009; 153: 347-358
• 32 Zephy D, Ahmad J. Type 2 diabetes mellitus: role of melatonin and oxidative stress. Diabetes & metabolic syndrome: clinical research & reviews 2015; 9: 127-131
• 33 Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxidative Medicine and Cellular Longevity. 2016; doi:10.1155/2016/3164734
• 34 Wirostko B, Wong TY, Simó R. Vascular endothelial growth factor and diabetic complications. Progress in retinal and eye research 2008; 27: 608-621
• 35 Perrotta F, Perna A, Komici K. et al. The State of Art of Regenerative Therapy in Cardiovascular Ischemic Disease: Biology, Signaling Pathways, and Epigenetics of Endothelial Progenitor Cells. Cells 2020; 9: 1886
• 36 Elbuluk A, Einhorn TA, Iorio R. A Comprehensive Review of Stem-Cell Therapy. Jbjs reviews 2017; 5: 1-15
• 37 Stancic A, Jankovic A, Korac A. et al. The role of nitric oxide in diabetic skin (patho) physiology. Mechanisms of Ageing and Development. 2018; 172: 21–29
• 38 Wan X, Liu S, Xin X. et al. S-nitrosated keratin composite mats with NO release capacity for wound healing. Chemical engineering journal 2020; 400: 125964
• 39 Yin Y, Li X, He X. et al. Leveraging Stem Cell Homing for Therapeutic Regeneration. Journal of dental research 2017; 96: 601-609