Contributions
Abstract: P1110
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Autologous bone marrow-derived mesenchymal stem cell-neural progenitors (MSC-NPs) are currently undergoing clinical testing as a reparative cell therapy strategy in patients with progressive multiple sclerosis (MS). The recently completed phase I clinical trial suggested that repeated intrathecal (IT) dosing of MSC-NPs was associated with improved motor strength and bladder function in the majority of study subjects. Preclinical studies have described the trophic and immunomodulatory effects of MSC-NPs both in vitro and in the EAE animal model of MS.
Objectives: To identify cerebrospinal fluid (CSF) biomarkers of clinical response to intrathecal MSC-NP treatment in patients with progressive MS.
Methods: MSC-NPs were isolated and expanded from bone marrow of 20 study participants enrolled in the phase I clinical trial. Gene expression of candidate trophic and immuomodulatory factors were analyzed in both MSCs and MSC-NPs by quantitative PCR. Secreted protein levels in conditioned media were quantitated by ELISA and by luminex assays. Potential biomarkers were also evaluated in CSF collected and banked at each of the 3 IT-MSC-NP treatments (3 months apart) as well as 3 months post 3rd treatment. Responders and non-responders to the treatment were categorized based on a sustained improvement in EDSS.
Results: Candidate trophic/immunomodulatory factors including HGF and CXCL12 were expressed and secreted at high levels in MSC-NPs and were increased in CSF after MSC-NP treatments over time. Baseline CSF levels of chitinase 3 like protein-1 (CHI3L1), a pro-inflammatory biomarker, were elevated in patients who did not show any change in EDSS after IT-MSC-NP treatment. In addition, CSF levels of the chemokine CCL2 were significantly reduced and neurodegenerative biomarkers neurofilament light and heavy were unchanged by IT-MSC-NP treatment.
Conclusions: These results help elucidate the trophic and immunomodultory mechanisms of IT-MSC-NP treatment and identify novel biomarkers of stem cell-mediated neural repair.
Disclosure: Violaine K. Harris: nothing to disclose
John Tuddenham: nothing to disclose
Shayna Zanker: nothing to disclose
Tamara Vyshkina: nothing to disclose
Saud A. Sadiq: nothing to disclose
Abstract: P1110
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Autologous bone marrow-derived mesenchymal stem cell-neural progenitors (MSC-NPs) are currently undergoing clinical testing as a reparative cell therapy strategy in patients with progressive multiple sclerosis (MS). The recently completed phase I clinical trial suggested that repeated intrathecal (IT) dosing of MSC-NPs was associated with improved motor strength and bladder function in the majority of study subjects. Preclinical studies have described the trophic and immunomodulatory effects of MSC-NPs both in vitro and in the EAE animal model of MS.
Objectives: To identify cerebrospinal fluid (CSF) biomarkers of clinical response to intrathecal MSC-NP treatment in patients with progressive MS.
Methods: MSC-NPs were isolated and expanded from bone marrow of 20 study participants enrolled in the phase I clinical trial. Gene expression of candidate trophic and immuomodulatory factors were analyzed in both MSCs and MSC-NPs by quantitative PCR. Secreted protein levels in conditioned media were quantitated by ELISA and by luminex assays. Potential biomarkers were also evaluated in CSF collected and banked at each of the 3 IT-MSC-NP treatments (3 months apart) as well as 3 months post 3rd treatment. Responders and non-responders to the treatment were categorized based on a sustained improvement in EDSS.
Results: Candidate trophic/immunomodulatory factors including HGF and CXCL12 were expressed and secreted at high levels in MSC-NPs and were increased in CSF after MSC-NP treatments over time. Baseline CSF levels of chitinase 3 like protein-1 (CHI3L1), a pro-inflammatory biomarker, were elevated in patients who did not show any change in EDSS after IT-MSC-NP treatment. In addition, CSF levels of the chemokine CCL2 were significantly reduced and neurodegenerative biomarkers neurofilament light and heavy were unchanged by IT-MSC-NP treatment.
Conclusions: These results help elucidate the trophic and immunomodultory mechanisms of IT-MSC-NP treatment and identify novel biomarkers of stem cell-mediated neural repair.
Disclosure: Violaine K. Harris: nothing to disclose
John Tuddenham: nothing to disclose
Shayna Zanker: nothing to disclose
Tamara Vyshkina: nothing to disclose
Saud A. Sadiq: nothing to disclose