Background: There is evidence that stem cells contribute to the restoration of tissue vascularization and organ function. The objective of this study was to assess the presence of adipose-derived adult stem cells left in their natural scaffold in the purified lipoaspirate and to assess the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects. Methods: This study was designed beginning with surgical procedures in 2002 and envisaging a continuous patient follow-up to 31 months. Twenty consecutive patients undergoing therapy for side effects of radiation treatment with severe symptoms or irreversible function damage (LENT-SOMA scale grade 3 and 4) were enrolled. Purified autologous lipoaspirates (60 to 120 cc) taken from a healthy donor site were administered by repeated low-invasive computer-assisted injection. Therapy outcomes were assessed by symptoms classification according to the LENT-SOMA scale, cytofluorimetric characterization, and ultrastructural evaluation of targeted tissue. Results: In the isolated stromal vascular fraction of 2 cc of human lipoaspirate, cells with mesenchymal stem cell physical properties and immunophenotype were in average 1.07 ± 0.5 percent (n = 4), with a clonogenic fraction of 0.139 percent. At least 1.02 × 10³ colony-forming units–fibroblast were present in each lipoaspirate. Ultrastructure of target tissue systematically exhibited progressive regeneration, including neovessel formation and improved hydration. Clinical outcomes led to a systematic improvement or remission of symptoms in all evaluated patients, including otherwise untreatable patients exhibiting initial irreversible functional damage. Conclusions: This surgical procedure is a low-invasive therapeutic approach for resolving the late side effects of radiotherapy. According to the proposed hypothesis of the ischemic nature of radiolesions, treatment with lipoaspirate transplantation is potentially extended to other forms of microangiopathies.

Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSCs induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSCs (ASCs) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASCs preferentially home into lymphoid organs but also migrates inside the central nervous system (CNS). Most importantly, administration of ASCs in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASCs expresses activated α4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that α4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor, and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASCs have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuroregeneration by endogenous progenitors in animals with established disease. Overall, our data suggest that ASCs represent a valuable tool for stem cell–based therapy in chronic inflammatory diseases of the CNS.

Adult mesenchymal stem cells derived from adipose tissue (A-MSC) have the capacity to differentiate in vitro into mesenchymal as well as endodermal and ectodermal cell lineages. We investigated the neuronal differentiation potential of human A-MSC with a protocol which included sphere formation and sequential culture in brain-derived neurotrophic factor (BDNF) and retinoic acid (RA). After 30 days, about 57% A-MSC showed morphological, immunocytochemical and electrophysiological evidence of initial neuronal differentiation. In fact, A-MSC displayed elongated shape with protrusion of two or three cellular processes, selectively expressed nestin and neuronal molecules (including GABA receptor and tyroxine hydroxilase) in the absence of glial phenotypic markers. Differentiated cells showed negative membrane potential (-60 mV), delayed rectifier potassium currents and TTX-sensitive sodium currents. Such changes were stable for at least 7 days after removal of differentiation medium. In view of these results and the easy availability of adipose tissue, A-MSC may be a ready source of adult MSC with neuronal differentiation potential, an useful tool to treat neurodegenerative diseases.

Ozone (O₃) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O₃ is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O₃ exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O₃ concentrations induce a moderate oxidative eustress activating antioxidant pathways. These properties make O₃ a powerful medical tool, which can be used as either a disinfectant or an adjuvant agent in the therapy of numerous diseases. In this paper, the cellular mechanisms involved in the antioxidant response to O₃ exposure will be reviewed with special reference to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role in the efficacy of ozone therapy.