Personalized‐induced neural stem cell therapy: Generation, transplant, and safety in a large animal model

Background: Chronic Kidney Disease (CKD) is an independent risk factor for cardiovascular morbidity and mortality. Left ventricular (LV) hypertrophy and heart failure with preserved ejection fraction (HFpEF) are the primary manifestations of the cardiorenal syndrome in 60 to 80% of CKD patients. Therapies that improve morbidity and mortality in HFpEF are lacking. Stem cell therapy reduces fibrosis, increases neovascularization, and promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that stem cell treatment ameliorates HFpEF in a CKD model. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: allogeneic (allo-) MSC (10х10 6 ), allo-kidney c-kit + cells (c-kit; 10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Cell therapy was delivered via the patent renal artery. Kidney function, renal and cardiac MRI, and PV loops were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was confirmed by increased creatinine and BUN and decreased GFR. Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks (p=0.7). HFpEF was demonstrated at 4 weeks by increased LV mass (20.3%; p= 0.0001), wall thickening (p<0.008), EDP (p=0.01), EDPVR (p=0.005), and arterial elastance (p=0.03), with no change in EF. Diffuse intramyocardial fibrosis was evident in histological analysis and delayed enhancement MRI imaging. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). GFR significantly improved in the combination group (p=0.033). EDV increased in the placebo (p=0.009) and c-kit (p=0.004) groups. ESV increased most in the placebo group (7.14±1.62ml; p=0.022). EF, wall thickness, and LV mass did not differ between groups at 12 weeks. Conclusion: A CKD large animal model manifests the characteristics of HFpEF. Intra-renal artery allogeneic cell therapy was safe. A beneficial effect of cell therapy was observed in the combination and MSC groups. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.

Abstract TP140: Intra-Arterial Mesenchymal Stem Cell Therapy Modulates Expression of NLRP1 Inflammasome in Animal Model of Ischemic Stroke

Stroke ◽

10.1161/str.50.suppl_1.tp140 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Deepaneeta Sarmah ◽

Kanchan Vats ◽

Jackson Saraf ◽

Harpreet Kaur ◽

Kiran Kalia ◽

...

Keyword(s):

Animal Model ◽

Stem Cell ◽

Ischemic Stroke ◽

Mesenchymal Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Mesenchymal Stem Cell Therapy ◽

Nlrp1 Inflammasome

Neural Stem Cell Therapy for Temporal Lobe Epilepsy

Jasper's Basic Mechanisms of the Epilepsies ◽

10.1093/med/9780199746545.003.0085 ◽

2012 ◽

pp. 1098-1110 ◽

Cited By ~ 5

Author(s):

Ashok K. Shetty

Keyword(s):

Stem Cell ◽

Cell Therapy ◽

Temporal Lobe Epilepsy ◽

Neural Stem Cell ◽

Temporal Lobe ◽

Stem Cell Therapy