Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia

Abstract

Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner. AdSCs inhibited the production of pro-inflammatory cytokines such as TNF-α and IL-12 in activated macrophages, and AdSCs also induced the apoptosis of activated macrophages. AdSCs inhibited the differentiation and proliferation of Th2-type mCD4+ T cells but promoted the differentiation and proliferation of regulatory T cells, suggesting that the phenotypic conversion of T cells may be one of the mechanisms for the anti-inflammatory effect of AdSCs on pulmonary fibrosis. These findings suggest that intravenous AdSCs could be a promising treatment for patients with interstitial pneumonia.

Local transplantation of adipose-derived stem cells has a significant therapeutic effect in a mouse model of rheumatoid arthritis

“…It would be more appropriate to use human ADSCs from a clinical perspective. However, previous studies on ADSCs have demonstrated their effectiveness across several species [33][34][35] . Second, the severity of RA in our mouse model was evaluated on the basis of generalized clinical scoring.…”

“…Adipose tissue was harvested from the inguinal region and used in all experiments as subcutaneous white adipose tissue. ADSCs were isolated from adipose tissue based on a previously described procedure 37 with slight modifications 35,38 . Briefly, adipose tissue harvested from mice subcutaneous area was washed in PBS, minced, and digested in 5 mL of type VIII collagenase (1 mg/mL in 1% BSA/HBSS; Life Technologies Japan, Tokyo, Japan) for 40 min at 37 °C using a Bioshaker BR15 (TAITEC, Tokyo, Japan) in accordance with the manufacturer's instructions.…”

Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

“…Adipose‐tissue‐derived stromal/stem cells are attracting much interest because they are pluripotent somatic stem cells capable of repairing an impaired organ, not only because of their ability to differentiate into miscellaneous cell types but also because of their ability to modulate inflammation, which is harmful to organs. The immunomodulatory effects of ADSCs are attractive, as the consequences are favorable in suppressing inflammation . Miscellaneous etiologies of chronic liver diseases, such as hepatitis B or hepatitis C infection, autoimmune hepatitis, and primary biliary cholangitis, are well known, and the immunopathological features differ among these etiologies.…”

“…The immunomodulatory effects of ADSCs are attractive, as the consequences are favorable in suppressing inflammation. 28 Miscellaneous etiologies of chronic liver diseases, such as hepatitis B or hepatitis C infection, autoimmune hepatitis, and primary biliary cholangitis, are well known, and the immunopathological features differ among these etiologies. The current study sheds light on the role of IL-17 in the development of NASH.…”

Cell Therapy in Idiopathic Pulmonary Fibrosis†

“…Adipose-mesenchymal stem cells have also been evaluated in some interesting studies [ 20 , 21 , 22 ]. Thashiro and colleagues studied the differences between young or old donor adipose-MSCs in old mice after 24 h of BLM instillation [ 20 ].…”