RESUMEN
Diabetes is a chronic degenerative disease that carries multiple complications. One of the most important complications is the diabetic cutaneous complications, such as skin lesions, ulcerations, and diabetic foot, which are present in 30%-70% of the patients. Currently, the treatments for wound healing include growth factors and cytokines, skin substitutes, hyperbaric oxygen therapy, and skin grafts. However, these treatments are ineffective due to the complex mechanisms involved in developing unhealed wounds. Considering the aforementioned complications, regenerative medicine has focused on this pathology using stem cells to improve these complications. However, it is essential to mention that there is a poor biomolecular understanding of diabetic skin and the effects of treating it with stem cells. For this reason, herein, we investigated the employment of pluripotent stem cells (PSC) in the wound healing process by carrying out morphometric, histological, and Fourier-transform infrared microspectroscopy (FTIRM) analysis. The morphometric analysis was done through a photographic follow-up, measuring the lesion areas. For the histological analysis, hematoxylin & eosin and picrosirius red stains were used to examine the thickness of the epidermis and the cellularity index in the dermis as well as the content and arrangement of collagen type I and III fibers. Finally, for the FTIRM analysis, skin cryosections were obtained and analyzed by employing a Cassegrain objective of 16× of an FTIR microscope coupled to an FTIR spectrometer. For this purpose, 20 mice were divided into two groups according to the treatment they received: the Isotonic Salt Solution (ISS) group and the PSCs group (n = 10). Both groups were induced to diabetes, and six days after diabetes induction, an excisional lesion was made in the dorsal area. Furthermore, using microscopy and FTIRM analysis, the skin healing process on days 7 and 15 post-skin lesion excision was examined. The results showed that the wound healing process over time, considering the lesion size, was similar in both groups; however, the PSCs group evidenced hair follicles in the wound. Moreover, the histological analysis evidenced that the PSCs group exhibited granulation tissue, new vessels, and better polarity of the keratinocytes. In addition, the amount of collagen increased with a good deposition and orientation, highlighting that type III collagen fibers were more abundant in the PSCs. Finally, the FTIR analysis evidenced that the PSCs group exhibited a faster wound healing process. In conclusion, the wounds treated with PSCs showed a more rapid wound healing process, less inflammatory cellular infiltration, and more ordered structures than the ISS group.
RESUMEN
Background: Breast cancer in men is a rare and poorly studied disease, and its treatment is based on women breast cancer studies. However, clinical outcome is not the same in men and women. Basic studies and clinical trials in animal models provide detailed information on cancer, origin, development, cell signaling pathways, sites of metastasis, and target molecules. It is necessary to explore the biology of breast cancer in male animal models that allow observing their similarity. Methods: The triple-negative 4T1 breast cancer model was developed in both male and female mice and studied weekly during 4 weeks. For that, twenty 8-week-old female and male BALB/c mice were used. Sixteen mice (eight males and eight females) were inoculated into the second left thoracic mammary pad with 20,000 4T1 cells, resuspended in 20 µL phosphate-buffered saline (PBS). All samples were processed for immunodetection, characterized histopathologically and immunohistochemically. Results: In this work, we describe the development of a triple-negative 4T1 breast cancer model in male BALB/c mice. Breast tumors were characterized histopathologically at different time points and corresponded to a moderately differentiated invasive ductal carcinoma, estrogen receptor ER-/progesterone receptor PR-/human epidermal growth factor receptor 2 HER2-/Ki67+, with histological grade II (moderately differentiated; a solid mass with occasional duct formation and moderate to severe nuclear pleomorphism), infiltrating the adipose and muscular tissue, and metastasis to lungs. From the results, we did not observe differences in the time of tumor development, necrosis, color change of tumor tissue, and lung metastasis between male and female mice. Even though we did not find histological differences, response to treatment and molecular signaling may be different. Conclusions: The histogenesis of male breast tumors was similar to that of female BALB/c mice. The histological and immunohistochemical characteristics of male tumors also match the features reported for stage IV human breast cancer of men and women. The murine male breast cancer model described here can be a significant tool to explore the molecular mechanisms involved in male breast cancer tumorigenesis and metastasis and may bring new approaches for clinical treatment of triple-negative breast cancer in men.
RESUMEN
Kidney diseases are a global public health problem. Despite significant advances in the understanding of renal failure (RF) and replacement therapies, this condition carries a series of complications and the life's quality of patients decreases. Differentiation capability of stem cells and their beneficial effects when they are implanted in animal models have been reported. Therefore, this work aimed to induce a long-term RF in mice, evaluating the biochemical and histological effects after implanting mouse embryonic stem cells (mESC). Mice were subjected to renal failure induction (RFI) employing cisplatin, subsequently received intraperitoneal (i.p.) injections of salt solution (control group, n=19) or 50 000 mESC (experimental group, n=19) at 24 hours, 7 days, and 13 days post-RFI. Ten animals in each group were used to analyze functional damage through serum biochemical analysis, and the mortality. For histopathological examination, three animals of each group were sacrificed at 5, 10, and 20 days post-RFI, analyzing the tubular system and glomeruli. Both groups showed blood urea nitrogen (BUN) and creatinine elevation three days post-RFI. Accumulated mortality was lower in the experimental group, presenting statistical significance. Respect to histopathological effects, the control group showed tubular dilatation, segmental focal glomerulosclerosis data, and collapsed glomeruli, while in the experimental group, glomerulosclerosis or collapsed glomeruli were not observed, evidencing regenerative data as characterized by large nuclei with prominent and binucleate nucleoli. In conclusion, mESC implant in mice with RFI significantly decreased the mortality, avoiding a greater histological deterioration related to the disease.
