Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model

Abstract

Background. Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods. Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results. rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion. Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.

Distinctive mesenchymal-like neurofibroma stem cells shape NF1 clinical phenotypes controlled by BDNF microenvironment

“…Collagen gels loaded with BDNF neutralizing antibodies significantly reduced the formation of axon branches after facial nerve transection in rats without significant adverse effects on neuronal survival and axon elongation [44] .Rat cell Saics (rCellSaics) derived from bone marroe-derived MSC (rBMSCs) have a higher potential to secrete neurotrophic factors. Intracerebral transplantation of CellSaics is beneficial to neural recovery in chronic intracerebral hemorrhage models, and this effect can be reversed by BDNF neutralizing antibodies [45] . Our study suggests that the BDNF neutralizing antibody is a promising drug for the treatment of type I neurofibroma.…”

Stem Cell Therapies for Intracerebral Hemorrhage: Review of Preclinical and Clinical Studies

“…Takamiya et al 60 recently reported that MSCs compounded with a biodegradable scaffold (CellSaic) resulted in better functional recovery than MSCs alone in a chronic ICH model. CellSaic released higher amounts of trophic factors such as BDNF, HGF, vascular endothelial growth factor (VEGF), and GDNF; extracellular vesicles (exosome) were also released in CellSaic.…”