The Effect of Injection of Fibroblast Cells Isolated from Foreskin on Histological Improvement of Diabetic Wound in Animal Model

فصلنامه زیست شناسی جانوری

Volume 14, Issue 2, January 2022, Pages 95-105   

Document Type: Original Articles

DOI: 10.22034/ascij.2021.687834

Authors

Abbas Zabihi¹; Rahim Ahmadi^{* 1, 2}; Atefe Dehghani¹

¹Department of Biology, Hamadan Branch, Islamic Azad University, Hamadan, Iran.

²Department of Biology, Ovinsina International College, Budapest, Hungary

Abstract

Despite a number of experimental studies, the healing effects of stem cells on chronic wounds still face serious challenges. The present study investigated the effect of injection of fibroblasts isolated from foreskin on the histological improvement of diabetic wounds in male rats. 24 male Wistar rats were divided into control and treatment groups during this experimental laboratory study.  Diabetes was induced in control and treatment groups using streptozotocin. Using a biopsy punch, a wound was created in the dorsal region of the animals Foreskin derived fibroblasts were injected into the dermis layer in the treatment group. On days 7, 14, and 21 after treatment, the wound healing was evaluated using morphologic observation, histological examination through hematoxylin- eosin staining, and measuring the wound size by Image j. On day 14 after treatment, the wound area was significantly smaller in the treated group than the control group (P<0.001). Histological examination showed that the skin thickness significantly increased in the treatment group on days 14 and 21 compared with control group (P<0.01). Besides, no morphologic complications were observed in the skin tissue following the injection of fibroblast cells. Our findings indicated that fibroblast cells are capable of accelerating the process of diabetic wound healing without morphologic complications in the skin tissue; according to which, the foreskin derived fibroblast cells can be used in the field of cell therapy. 
 

Keywords

Fibroblasts; Foreskin; Diabetic wound; Hematoxylin-Eosin; Rat

References

1- Afessa B., Peters S.G. 2006. Major complications following hematopoietic stem cell transplantation. In seminars in respiratory and critical care medicine, 27(3): 297.

2- Arnaout K., Patel N., Jain M., El-Amm J., Amro F., Tabbara I.A. 2014. Complications of allogeneic hematopoietic stem cell transplantation. Cancer investigation, 32(7): 349-62.

3- Bainbridge P. 2013. Wound healing and the role of fibroblasts. Journal of wound care, 22(8): 407-11.

4- Belvedere R., Pessolano E., Porta A., Tosco A., Parente L, Petrella F., Perretti M., Petrella A. 2020. Mesoglycan induces the secretion of microvesicles by keratinocytes able to activate human fibroblasts and endothelial cells: A novel mechanism in skin wound healing. European Journal of Pharmacology, 869: 172894.

5- Blair M. Diabetes Mellitus Review.2016. Urologic nursing, 36(1): 27-36.

6- Bus S.A., Lavery L.A., Monteiro‐Soares M., Rasmussen A., Raspovic A., Sacco I.C., van Netten J.J. 2020. International Working Group on the Diabetic Foot. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes/metabolism research and reviews, 36: e3269.

7- Deb A., Ubil E. 2014.Cardiac fibroblast in development and wound healing. Journal of molecular and cellular cardiology, 70: 47-55.

8- Desjardins-Park HE, Foster DS, Longaker MT. 2018. Fibroblasts and wound healing: an update, 13(5):491– 95.

9- Esteghamati A., Larijani B., Aghajani M.H., Ghaemi F., Kermanchi J, Shahrami A., Saadat M., Esfahani E.N., Ganji M., Noshad S., Khajeh E. 2017. Diabetes in Iran: prospective analysis from first nationwide diabetes report of National Program for Prevention and Control of Diabetes (NPPCD-2016). Scientific Reports,7(1):1-0.

10- Hanson S.E., Bentz M.L., Hematti P. Mesenchymal stem cell therapy for nonhealing cutaneous wounds. 2010. Plastic and reconstructive surgery, 125(2): 510.

11- Hocking A.M. 2012. Mesenchymal stem cell therapy for cutaneous wounds. Advances in wound care, 1(4): 166-171.

12- Harding J.L., Pavkov M.E., Magliano D.J., Shaw J.E., Gregg E.W. 2019. Global trends in diabetes complications: a review of current evidence. Diabetologia, 62(1): 3-16.

13- Hu X., Zhang H., Li X., Li Y., Chen Z. 2020. Activation of mTORC1 in fibroblasts accelerates wound healing and induces fibrosis in mice. Wound Repair and Regeneration, 28(1): 6-15.

14- Katz M.H., Alvarez A.F., Kirsner R.S., Eaglstein W.H., Falanga V. 1991. Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. Journal of the American Academy of Dermatology, 25(6): 1054-8.

15-  León C., García-García F., Llames S., García-Pérez E., Carretero M., Arriba M.D., Dopazo J., Del Río M., Escámez M.J., Martínez-Santamaría L. 2021. Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response. Genes, 12(1): 47.

16- Li Y., Xia W.D., Van der Merwe L., Dai W.T., Lin C. 2020. Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies. Stem cell research and therapy, 11(1): 1-2.

17- Lotfy M., Adeghate J., Kalasz H., Singh J., Adeghate E. 2017. Chronic complications of diabetes mellitus: a mini review. Current diabetes reviews, 13(1): 3-10.

18- McDougall S., Dallon J., Sherratt J., Maini P. 2006. Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 364(1843): 1385-1405.

19- Momeni Moghaddam M, Vatandoost J. 2017. Mouse skin wound healing using Lucilia sericata maggot extract. Journal of Cellular and Molecular Research (Iranian Journal of Biology, 30(1): 26-39.

20- Monfared GS, Ertl P, Rothbauer M. 2020. An on-chip wound healing assay fabricated by xurography for evaluation of dermal fibroblast cell migration and wound closure. Scientific reports, 10(1): 1-4.

21- Nilforoushzadeh MA, Jaffary F, Siavash M, Heidari A, Ansari N, Hossein Siadat A. 2015. Treatment of recalcitrant diabetic ulcers with trichloroacetic acid and fibroblasts: Case report. Journal of Isfahan Medical School, 32(315): 2252-2259.

22- Oh EJ, Gangadaran P, Rajendran RL, Kim HM, Oh JM, Choi KY, Chung HY, Ahn BC. 2020. Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions. Stem Cells, 39(3): 266-279.

23- Rajendran NK, Houreld NN, Abrahamse H. 2020. Photobiomodulation reduces oxidative stress in diabetic wounded fibroblast cells by inhibiting the FOXO1 signaling pathway. Journal of Cell Communication and Signaling, 14:1-2.

24- Ray J.A., Valentine W.J., Secnik K., Oglesby A.K., Cordony A., Gordois A., Davey P., Palmer A.J. 2005.  Review of the cost of diabetes complications in Australia, Canada, France, Germany, Italy and Spain. Current medical research and opinion, 21(10): 1617-1629.

25- Saha J.K., Xia J., Grondin J.M., Engle S.K., Jakubowski J.A. 2005. Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models. Experimental Biology and Medicine, 230(10): 777-784.

26-  Saheli M, M, Ganji R, Hendudari F, Kheirjou R, Pakzad M, Najar B, Piryaei A. 2020. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Archives of dermatological research, 312(5): 325-336.

27-  Suhaeri M., Noh M.H., Moon J.H., Kim I.G., Oh S.J., Ha S.S., Lee J.H., Park K. 2018. Novel skin patch combining human fibroblast-derived matrix and ciprofloxacin for infected wound healing. Theranostics, (18): 5025.

28- Wu Y., Chen L, Scott P.G., Tredget E.E. 2007. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem cells, 25(10): 2648-2659.

29-  Xu J., Wu W., Zhang L., Dorset-Martin W., Morris M.W., Mitchell M.E., Liechty K.W. 2012. The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment. Diabetes, 61(11): 2906-2912.

30- Yin J., Jurkunas U. 2018. Limbal stem cell transplantation and complications. InSeminars in ophthalmology. 33(1): 134-141.