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Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice.
Regmi, Shobha; Pathak, Shiva; Chaudhary, Dinesh; Kim, Jong Oh; Nam, Joo-Won; Kim, Hyung-Sik; Jiang, Hu-Lin; Ryu, Dongryeol; Sung, Jong-Hyuk; Yook, Simmyung; Jeong, Jee-Heon.
Afiliação
  • Regmi S; College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
  • Pathak S; Interventional Radiology Innovation at Stanford, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94304, USA.
  • Chaudhary D; College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
  • Kim JO; Division of Blood and Marrow Transplantation, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • Nam JW; Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • Kim HS; College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
  • Jiang HL; College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
  • Ryu D; Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea.
  • Sung JH; Dental and Life Science Institute, Pusan National University, Yangsan, 50612, Republic of Korea.
  • Yook S; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
  • Jeong JH; Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing, 210009, China.
Stem Cell Res Ther ; 15(1): 167, 2024 Jun 13.
Article em En | MEDLINE | ID: mdl-38872206
ABSTRACT

BACKGROUND:

Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases.

METHODS:

Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR.

RESULTS:

The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process.

CONCLUSION:

This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzilaminas / Sulfato de Dextrana / Tacrolimo / Colite / Ciclamos / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzilaminas / Sulfato de Dextrana / Tacrolimo / Colite / Ciclamos / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2024 Tipo de documento: Article
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