자가면역질환

Anti-inflammatory Effects of Oct4/Sox2-overexpressing Human Adipose Tissue-derived Mesenchymal Stem Cells

Background/Aim: The transcription factors Oct4
and Sox2 enhance the proliferation and pluripotency of
human adipose tissue-derived mesenchymal stem cells (hATMSCs);
however, the anti-inflammatory effects of Oct4- and
Sox2-overexpressing hAT-MSCs (Oct4/Sox2-hAT-MSCs) are
unclear. Here, we evaluated the anti-inflammatory effects of
Oct4/Sox2-hAT-MSCs in vitro and in vivo.

Accordingly, in this study, the anti-inflammatory effects
of lentivirus-transduced Oct4/Sox2-hAT-MSCs were
investigated by determining the expression of
inflammation-related cytokines in macrophage cell lines
treated with conditioned medium in vitro. In addition,
sickness scores (diarrhea, eye condition, activity and fur
condition) and survival rates were used to evaluate the antiinflammatory
effects of the engineered hAT-MSCs in a
mouse model.

Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells.

요약 : 
Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that exvivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here