**14. Conclusion**

**12. Fat graft and ADSC application for breast tissue regeneration**

increased fat graft microvasculature.

130 Tissue Regeneration

Masuda and colleagues [63] in their report demonstrated that transplanted omental tissue both in the presence and absence of pre-adipocytes isolated from epididymal adipose tissues under the dorsal skin of Wistar rats after 12 weeks efficiently produced high levels of triacylglycerol content, capillary density, and VEGF. They concluded that co-transplantation with pre-adipocytes significantly accelerated adipose tissue formation. In another study by Matsumoto and co-workers [64], they reported that cell-assisted lipotransfer (CAL) fat had an increased survival rate than non-CAL fat, and there were early signs of microvasculature in CAL fat. Moseley and colleagues [65] using a nude mice showed that fat supplemented with ASCs sustained its adipocyte-rich appearance and weighed 2.5× greater compared to non-ASC supplemented grafted fat. Furthermore, Zhu and co-workers reported comparable findings that fat grafts treated with ASCs increase capillary density and neovascularization [66]. Several studies have also reported that cultured human ASCs produce and release several angiogenic growth factors under hypoxia condition [67, 68] and have been associated with

Coleman and colleagues in a retrospective study of 17 breast procedures done from 1995 to 2000 reported that all patients had a significant enhancement in their breast size and shape postoperatively [69]. Coleman and colleagues stated that most patients in their study underwent mammography a year after breast surgery without any known screening complications. Yoshimura and colleagues [70] in their clinical study did CAL on six patients with facial lipoatrophy. The authors concluded that the CAL group had a better clinical improvement score compared to the non-CAL patients. In another related study by Yoshimura and colleagues [71], they conducted two clinical trials, using CAL for breast reconstruction. Yoshimura et al. concluded that after treatment of 55 patients, there was advancement in the clinical results with evidences of graft retention. In addition, reconstruction and retention outcomes were

demonstrated by Kitamura and co-workers [72] after CAL treatment in five patients.

with breast implants and/or myocutaneous flaps [74].

**13. ASCs and skin tissue engineering**

In a more recent clinical study by Tissiani and Alonso [73], they investigated the effectiveness of autologous fat grafts supplemented with stromal vascular fraction (SVF) in secondary breast reconstruction surgery. The authors concluded that after 3 years of follow-up of the patients they proved volumetric persistence of this type of fat tissue grafts without any significant clinical complications recorded. In another clinical study by Claro and colleagues, it was reported that the complication rate after autologous fat tissue grafting was low compared to the complication rate after breast reconstruction surgery procedures done

Böttcher-Haberzeth and colleagues have extensively reported the development of a skin substitute known as tissue-engineered dermo-epidermal skin substitutes (DESS). It is made of the two basic native skin layers, epidermal and dermal layers, and it can potentially serve as a Scaffold-based tissue engineering using stem cells has improved the field of tissue regeneration in medicine; however, it is still at the infancy level. An extensive in-depth scientific knowledge and study of different stem cells will go a long way to translate them to clinical application. In addition, more extensive studies are needed to be done on different scaffold designs because the success of tissue engineering depends on these scaffolds and provides a niche to transplanted cells. Furthermore, most of the use of stem cells in tissue regeneration has been directed toward small tissue defect as such efforts to develop bioengineered grafts to repair larger tissue defects (bone defects) should be made. Several stem cells like induced pluripotent stem cell, mesenchymal stem cells, and ASCs are promising source of patientspecific stem cells with great regenerative potential. However, few or no clinical translation is available as they are potential teratoma and carcinogenic causative agents, and isolation of some of these cells is deemed unethical. Stem cells seeded on decellularized scaffolds have been reported to demonstrate promising and excellent results over the years. However, more clinical evaluations are needed to be properly sure they are safe clinically.
