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. 2021 Sep 3;54(11):e11352.
doi: 10.1590/1414-431X2021e11352. eCollection 2021.

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats

G L Flores Luna  1 , T L Oehlmeyer  1 , G Brandão  1 , P Brassolatti  2 , J Tosta  1 , L S Goto  3 , L de Avó  4 , A M de Oliveira Leal  1
Affiliations

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats

G L Flores Luna et al. Braz J Med Biol Res. .

Abstract

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

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Figures

Figure 1
Figure 1. Experimental groups and study design. Five weeks after the confirmation of diabetes, skin lesions were performed and, immediately afterwards, an intracutaneous infusion of phosphate buffer solution (control group and diabetic rats wounded) or 1×106 human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) (C-TERT and DM-TERT groups) was performed. Fasting glycemia was determined weekly and photographic assessments of the wounds were performed on days 0, 3, 7, 14, and 21 days after the first infusion. STZ: streptozotocin.
Figure 2
Figure 2. Human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT). Passage five plastic-adherent cells cultured in α-MEM supplemented with 10% fetal bovine serum (A) and differentiated into adipogenic lineages identified by Sudan II (0.2%) (B), osteogenic lineages identified by von Kossa technique (C), and chondrogenic lineages identified by Alcian blue (1%) (D). Scale bar 100 μm.
Figure 3
Figure 3. Effects of human bone marrow mesenchymal cells immortalized by the expression of telomerase (hMSC-TERT) infusion on wound closure. A, Representative images of wounds in rats from the groups evaluated on days 0, 7, 14, and 21. B, Percentage of wound reduction in the healing area on days 0, 7, 14, and 21 post-injury. The data are reported as means±SD. CW: control rats wounded; C-TERT: non-diabetic rats wounded and infused with hBMSC-TERT; DMW: diabetic rats wounded; DM-TERT: diabetic rats wounded and infused with hBMSC-TERT.
Figure 4
Figure 4. Wound histological representative images stained by hematoxylin-eosin showing a collagen fiber (black arrow) (A), fibroblast (red arrow) (B), and inflammatory infiltrate (green arrow) (C). Scale bar 200 μm.
Figure 5
Figure 5. Score analysis of collagen (A), fibroblasts (B), and inflammatory cells (C) of skin wounds after treatment with human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT). Data are reported as means±SD for n=6-10 rats/group. *P<0.05 vs CW; †P<0.05 vs DMW (ANOVA). CW: control rats wounded; C-TERT: non-diabetic rats wounded and infused with hBMSC-TERT; DMW: diabetic rats wounded; DM-TERT: diabetic rats wounded and infused with hBMSC-TERT.
Figure 6
Figure 6. Quantitative birefringence analysis for the groups after treatment with human bone marrow mesenchymal cells immortalized by the expression of telomerase (hBMSC-TERT). White arrows indicate the birefringent fibers. Data are reported as means±SD. *P<0.05 vs CW; †P<0.05 vs DMW (ANOVA). Scale bar 100 μm. CW: control rats wounded; C-TERT: non-diabetic rats wounded and infused with hBMSC-TERT; DMW: diabetic rats wounded; DM-TERT: diabetic rats wounded and infused with hBMSC-TERT.
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