Background: During recent decades, multipotent stem cells were found to reside in the adipose tissue, and these adipose-derived stem cells were shown to play beneficial roles, like those of Schwann cells, in peripheral nerve regeneration. However, it has not been well established whether adipose-derived stem cells offer beneficial effects to peripheral nerve injuries in vivo as Schwann cells do. Furthermore, the in situ survival and differentiation of adipose-derived stem cells after transplantation at the injured peripheral nerve tissue remain to be fully elucidated. Methods: Adipose-derived stem cells and Schwann cells were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice. Neuroregenerative abilities of them were comparably estimated. Cre-loxP–mediated fate tracking was performed to visualize survival in vivo of transplanted adipose-derived stem cells and to investigate whether they differentiated into Schwann linage cells at the peripheral nerve injury site. Results: The transplantation of adipose-derived stem cells promoted regeneration of axons, formation of myelin, and restoration of denervation muscle atrophy to levels comparable to those achieved by Schwann cell transplantation. The adipose-derived stem cells survived for at least 4 weeks after transplantation without differentiating into Schwann cells. Conclusions: Transplanted adipose-derived stem cells did not differentiate into Schwann cells but promoted peripheral nerve regeneration at the injured site. The neuroregenerative ability was comparable to that of Schwann cells. Adipose-derived stem cells at an undifferentiated stage may be used as an alternative cell source for autologous cell therapy for patients with peripheral nerve injury.

Background: Breast reconstruction is a promising surgical technique to improve health-related quality of life (HRQoL) in patients with breast cancer. However, the long-term risk factors associated with HRQoL after breast surgery are still unclear. Our aim was to evaluate breast satisfaction and HRQoL following breast reconstruction to identify clinical factors associated with each domain of BREAST-Q in the long-term. Methods: Patient-reported BREAST-Q outcomes were analyzed 1 and 5 years after breast reconstruction in a single-blinded, prospective study. Multiple regression analysis was performed to identify the risk and protective factors associated with BREAST-Q scores. These scores at 1 and 5 years were also compared across three types of operation: mastectomy only, tissue expander/implant (TE/Imp), and a deep inferior epigastric perforator (DIEP) flap. Results: Surveys were completed by 141 subjects after 1 year and 131 subjects after 5 years. Compared to mastectomy only, breast reconstruction was significantly associated with greater “Satisfaction with breasts” (TE/Imp, p < 0.001; DIEP, p < 0.001) and “Psychosocial well-being” (TE/Imp, p < 0.001; DIEP, p < 0.001), higher body mass index (BMI) resulted in lower “Satisfaction with breasts” (p = 0.004), and a history of psychiatric or neurological medication was significantly associated with “Physical well-being” at 1-year postoperatively (p = 0.02). At 5 years, reconstructive procedures were significantly positively associated with greater “Satisfaction with breasts” (TE/Imp, p < 0.001; DIEP, p < 0.001) and “Psychosocial well-being” (TE/Imp, p = 0.03; DIEP, p < 0.001), and a bilateral procedure was a significant risk factor for lower “Psychosocial well-being” (p = 0.02). Conclusions: The results of this study show that breast reconstruction improves “Satisfaction with Breasts” and “Psychosocial well-being” compared to mastectomy. Among all three types of operation, DIEP gave the best scores at 5 years postoperatively. Thus, autologous reconstruction is recommended for promotion of long-term HRQoL after breast surgery.

Sowa Y, et al. Ann Surg Treat Res. 2017 Sep;93(3):119-124. https://doi.org/10.4174/astr.2017.93.3.119

The objective of this study was to identify response patterns related to sexual well-being following breast operations in the Japanese population. Patient-reported outcomes were analyzed at 1 year and 5 years after breast operations, including breast reconstruction, for Japanese women at a single center, with a focus on "Sexual well-being" in BREAST-Q. Response analysis and multiple regression analysis were performed. The scores at years 1 and 5 were also compared across three types of operation: mastectomy only, TE/Imp, and DIEP. The response rate for Sexual well-being on BREAST-Q in the prospective cohort of patients with breast cancer dropped from 60.0% in postoperative year 1-34.3% in year 5. The mean score for Sexual well-being increased from 32 (year 1) to 38 (year 5). There were significant differences between respondents and non-respondents in age at year 1 (P = 0.007) and for mastectomy only (P = 0.01) and TE/Imp (P = 0.03) at year 5. In regression analysis, only DIEP was positively associated with Sexual well-being at year 1 (p < 0.001) and there were no significant factors at year 5. Among the operative procedures, scores after DIEP were significantly better than those after mastectomy only at year 1 (p < 0.001), but there was no difference at year 5. There were no significant changes from year 1 to year 5 for each operation. A low response rate for Sexual well-being on BREAST-Q was found in Japanese women at 5 years postoperatively. This suggests the need for development of a modified evaluative scale that avoids nonresponse bias and considers ethnic differences.

This study presents a set of vibrational characterizations on a nanogel-cross-linked porous freeze-dried gel (NanoCliP-FD gel) scaffold for tissue engineering and regenerative therapy. This scaffold is designed for the in vitro culture of high-quality cartilage tissue to be then transplanted in vivo to enable recovery from congenital malformations in the maxillofacial area or crippling jaw disease. The three-dimensional scaffold for in-plate culture is designed with interface chemistry capable of stimulating cartilage formation and maintaining its structure through counteracting the dedifferentiation of mesenchymal stem cells (MSCs) during the formation of cartilage tissue. The developed interface chemistry enabled high efficiency in both growth rate and tissue quality, thus satisfying the requirements of large volumes, high matrix quality, and superior mechanical properties needed in cartilage transplants. We characterized the cartilage tissue in vitro grown on a NanoCliP-FD gel scaffold by human periodontal ligament-derived stem cells (a type of MSC) with cartilage grown by the same cells and under the same conditions on a conventional (porous) atelocollagen scaffold. The cartilage tissues produced by the MSCs on different scaffolds were comparatively evaluated by immunohistochemical and spectroscopic analyses. Cartilage differentiation occurred at a higher rate when MSCs were cultured on the NanoCliP-FD gel scaffold compared to the atelocollagen scaffold, and produced a tissue richer in cartilage matrix. In situ spectroscopic analyses revealed the cell/scaffold interactive mechanisms by which the NanoCliP-FD gel scaffold stimulated such increased efficiency in cartilage matrix formation. In addition to demonstrating the high potential of human periodontal ligament-derived stem cell cultures on NanoCliP-FD gel scaffolds in regenerative cartilage therapy, the present study also highlights the novelty of Raman spectroscopy as a non-destructive method for the concurrent evaluation of matrix quality and cell metabolic response. In situ Raman analyses on living cells unveiled for the first time the underlying physiological mechanisms behind such improved chondrocyte performance.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.