Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease

Abstract

Regenerative medicine for the treatment of motor features in Parkinson's disease (PD) is a promising therapeutic option. Donor cells can simultaneously address multiple pathological mechanisms while responding to the needs of the host tissue. Previous studies have demonstrated that mesenchymal stromal cells (MSCs) promote recovery using various animal models of PD. SanBio Inc. has developed a novel cell type designated SB623, which are adult bone marrow-derived MSCs transfected with Notch intracellular domain. In this preclinical study, SB623 cells protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal injury when transplanted unilaterally into C57BL/6 mouse striatum 3 days prior to toxin exposure. Specifically, mice with the SB623 cell transplants revealed significantly higher levels of striatal dopamine, tyrosine hydroxylase immunoreactivity and stereological nigral cell counts in the ipsilateral hemisphere vs vehicle-treated mice following MPTP administration. Interestingly, improvement in markers of striatal dopaminergic integrity was also noted in the contralateral hemisphere. These data indicate that MSCs transplantation, specifically SB623 cells, may represent a novel therapeutic option to ameliorate damage related to PD, not only at the level of striatal terminals (i.e. the site of implantation) but also at the level of the nigral cell body. Copyright © 2015 John Wiley & Sons, Ltd.

Mesenchymal stem cells as a multimodal treatment for nervous system diseases

“…There have also been studies with an established cell line, SB623 hBM‐MSCs (SanBio Inc.), which overexpresses the NOTCH 1 intracellular domain. These cells transplanted in preclinical trials have ameliorated damage in models of PD or after TBI, 105,106 probably due to enhanced neuropoietic and proangiogenic activity 107,108 . Moreover, in a TBI model, transplanted SB623 cells formed “biobridges” between the neurogenic niche and the site of injury 106 .…”

Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α‐synuclein, amyloid‐β and insulin resistance in neurodegenerative diseases

“…Evidently this generates essentially the same outcome, and from the literature for the same reasons, as does perispinal etanercept (Tobinick, ; Tobinick et al ., ). This is consistent with data from experimental PD, in which both SB623 cells (Tate et al ., ) and an anti‐TNF agent (Ferger et al ., ) have attenuated the toxicity of MPTP. As we have noted in our published correspondence regarding this text (Clark, ), with acceptance of the possibility from the authors (Steinberg et al ., ), the capacity of these stem cells to improve post‐stroke disabilities is most likely through creating a strong anti‐inflammatory milieu, generated in this case by FGF2 (Aizman et al ., ).…”

“…As with AD and PD, post‐stroke syndromes and TBI also manifest a predisposition to be more severe in APOE4 individuals (Eramudugolla et al ., ; Das et al ., ). Another set of observations transgressing these traditional clinical divides concerns the ability of SB623 stem cells, which manifest an anti‐TNF activity (see below) being efficacious for the PD model generated by injecting methylphenyltetrahydropyridine (MPTP) (Tate et al ., ) and in post‐stroke patients (Steinberg et al ., ).…”

Synergistic Therapeutic Effects of Intracerebral Transplantation of Human Modified Bone Marrow-Derived Stromal Cells (SB623) and Voluntary Exercise with Running Wheel in a Rat Model of Ischemic Stroke

“…Human modi ed bone marrow-derived MSCs, called SB623 cells, were produced by transient transfection of a plasmid encoding the human Notch-1 intracellular domain cDNA to bone marrow-derived MSCs obtained from a healthy young adult human donor (SanBio, Inc., Mountain View, CA, United States). SB623 cells were characterized by previous studies [11,29,30,31]. Yasuhara et al and Tate et al applied these cells to animal models of ischemic stroke and Parkinson's disease, respectively [10,31].…”

“…SB623 cells were characterized by previous studies [11,29,30,31]. Yasuhara et al and Tate et al applied these cells to animal models of ischemic stroke and Parkinson's disease, respectively [10,31].…”