**1. Introduction**

Adult stem cells have been used as the promising source of stem cells, which can be applied for cell-based therapies [1–3]. Among the adult stem cells, adipose-derived stem/progenitor cells (ADSCs) are the most promising ones, since they can be easily obtained from liposuction aspirates or subcutaneous adipose tissue fragments and expanded in vitro and there are no ethical concerns like human embryonic stem cells [4–9]. Furthermore, accumulating evidences have indicated that ADSCs showed multi-lineage di fferentiation, including classical mesenchymal lineages as well as non-mesenchymal ectodermal and endodermal lineages [1,10–12]. Recently, we have applied ADSCs for autologous transplantation therapy for chronic radiation injury [13]. ADSCs were obtained by less invasive lipoaspiration in combination with automatic and aseptic isolation. As ADSCs could be the e ffective component of transplanted fat tissue, which has been applied to wound repair and regeneration, ADSCs transplantation is expected to show equivalent e fficacy to fat tissue transplantation. Thus, ADSCs could be a critical and promising cell population in amending impaired subcutaneous adipose-tissue including lipodystrophy.

Lipodystrophy is characterized by either complete or partial loss of adipose tissue [14]. There are congenital and acquired lipodystrophy, and one representative acquired form occurs in human immunodeficiency virus (HIV)-infected individuals treated with highly active antiretroviral therapy (HAART), and up to 70% of patients receiving HAART are reported to have HIV-associated lipodystrophy. The HAART has been succeeded in inhibiting virus multiplication, and thus, it significantly improves the survival of HIV-infected patients [15–18]. However, as HIV-infected patients live longer, it became more evident that HAART induced multiple layers of adverse e ffects including adipose-tissue damage. Adipose-tissue damage manifests as abnormal distribution of adipose tissue, and clinical features of lipodystrophy include peripheral lipoatrophy and central lipohypertrophy [19–23].

It has been reported that lipodystrophy caused by nucleoside reverse transcriptase inhibitors (NRTIs) is related to its e ffect in mitochondria, which results in apoptosis induction in adipocytes [24–26]. Subsequently, NRTIs were substituted with protease inhibitors (PIs), and although PIs showed less effect on mitochondria than NRTIs, it becomes evident that PIs induce endoplasmic reticulum (ER) stress by accumulating unprocessed proteins in adipocytes, which are the inducer for unfolded protein response (UPR)-dependent apoptosis [27]. Thus, PIs have also brought about lipodystrophy in not a small number of the patients receiving HAART [28–31]. Previously, fat tissue transplantation was applied to lipodystrophy, particularly to facial lipodystrophy [32–34]. It e fficiently improved facial disfigurement, which resulted in improvement in patient's quality of life, however, it needed surgical excision of fat tissue. Therefore, ADSCs-based therapy should be more beneficial to the patients with severe lipodystrophy in comparison with the fat tissue transplantation alone, since it is minimally invasive. However, because lipodystrophy is closely related to dysfunction of di fferentiated adipocytes, and ADSCs are those supply adipocytes in tissue, irreversible and detrimental e ffects of HARRT on ADSCs could be a possible cause resulting in lipodystrophy [22,23]. Thus, it is inevitable to ascertain whether the ADSCs obtained from the patients with lipodystrophy are capable of being used, which could be tested in vitro.

ADSCs in HIV-infected patients could be obtained from abdomen, thighs, and shoulders, where lipoatrophy was less severe but apparently induced; but, a study has claimed that adipose tissue may be damaged not only by HAART but also by HIV-infection itself through the possible impairment of mitochondrial function [35]. Thus, in order to achieve successful ADSCs-based therapy, the current study aimed at determining whether ADSCs isolated from HIV-infected patients receiving HAART retain su fficient biological and physiological activities for reconstitution of subcutaneous adipose tissue. Total eight ADSCs were established from the subcutaneous lipoaspirates obtained from the donor sites, such as lower abdomen, thighs, buttocks, and shoulders, from three HIV-infected patients and four uninfected patients [36]. Growth properties, adipogenic di fferentiation, and mitochondrial ROS production were examined in ADSCs from HIV-infected and HIV-unrelated patients ex vivo. Our results clearly demonstrated that ADSCs from HIV-infected patients showed indistinguishable growth properties and potentials for adipocyte di fferentiation in vitro. Thus, although a number of cases was limited, ADSCs derived from the patients receiving HAART retain su fficient physiological and biological activity for the reconstitution of adipose-tissue, indicating that ADSCs from the patients with lipodystrophy could have su fficient biological potential so that they could be used for autologous ADSCs-based regenerative therapy.
