Dataset Information

Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid.

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a well-established method for a variety of acquired and congenital diseases. However, the limited number and sources of therapeutic hematopoietic stem/progenitor cells (HSPCs) hinder the further application of HSCT. A BMP-2 triggered in vivo osteo-organoid that is previously reported, serves as a kind of stem cell biogenerator, for obtaining therapeutic HSPCs via activating the residual regenerative capacity of mammals using bioactive biomaterials. Here, it is demonstrated that targeting the homing signaling of HSPCs elevates the proportions and biological functions of HSPCs in the in vivo osteo-organoid. Notably, it is identified that sulfonated chito-oligosaccharide, a degradation product of sulfonated chitosan, specifically elevates the expression of endothelial protein C receptor on HSPCs and vascular cell adhesion molecule-1 on macrophages in the in vivo osteo-organoid, ultimately leading to the production of adequate therapeutic HSPCs. This in vivo osteo-organoid approach has the potential to provide an alternative HSPCs source for HSCT and benefits more patients.

SUBMITTER: Dai K

PROVIDER: S-EPMC10460842 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid.

Dai Kai K Zhang Wenchao W Deng Shunshu S Wang Jing J Liu Changsheng C

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230625 24

Hematopoietic stem cell transplantation (HSCT) is a well-established method for a variety of acquired and congenital diseases. However, the limited number and sources of therapeutic hematopoietic stem/progenitor cells (HSPCs) hinder the further application of HSCT. A BMP-2 triggered in vivo osteo-organoid that is previously reported, serves as a kind of stem cell biogenerator, for obtaining therapeutic HSPCs via activating the residual regenerative capacity of mammals using bioactive biomaterial ...[more]

PMID: 37357138

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Project description:BackgroundExpansion of hematopoietic stem/progenitor cells (HSPCs) is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB) derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion.Methodology/principal findingsCB derived CD34(+) cells were expanded using a combination of growth factors with and without Caspase inhibitor -zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homing-related molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors) caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice.Conclusion/significanceOur present study reveals another novel aspect of the regulation of caspase and calpain proteases in the biology of HSPCs. The priming of the homing responses of the inhibitor-cultured HSPCs compared to the cytokine-graft suggests that the modulation of these proteases may help in overcoming the major homing defects prevalent in the expansion cultures thereby facilitating the manipulation of cells for transplant procedures.

Dataset Information

Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid.

Publications

Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid.

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