Laura A Galganski1, Priyadarsini Kumar2, Melissa A Vanover3, Christopher D Pivetti4, Jamie E Anderson5, Lee Lankford6, Zachary J Paxton7, Karen Chung8, Chelsey Lee9, Mennatalla S Hegazi10, Kaeli J Yamashiro11, Aijun Wang12, Diana L Farmer13. 1. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: lgalganski@ucdavis.edu. 2. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: pkumar@ucdavis.edu. 3. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: mvanover@ucdavis.edu. 4. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA; Shriners Hospitals for Children Northern California, 2425 Stockton Blvd, Sacramento, CA 95817, USA. Electronic address: cdpivetti@ucdavis.edu. 5. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: jeanderson@ucdavis.edu. 6. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: llankford@ucdavis.edu. 7. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: zjpaxton@ucdavis.edu. 8. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: kwxchung@ucdavis.edu. 9. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: chjlee@ucdavis.edu. 10. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: mshegazi@ucdavis.edu. 11. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA. Electronic address: kjyamashiro@ucdavis.edu. 12. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA; Shriners Hospitals for Children Northern California, 2425 Stockton Blvd, Sacramento, CA 95817, USA. Electronic address: aawang@ucdavis.edu. 13. University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA; Shriners Hospitals for Children Northern California, 2425 Stockton Blvd, Sacramento, CA 95817, USA. Electronic address: dlfarmer@ucdavis.edu.
Abstract
BACKGROUND: We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model. METHODS: PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 105 cells/cm2 of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale. RESULTS: In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs. CONCLUSION: The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use. LEVEL OF EVIDENCE: n/a. TYPE OF STUDY: Basic science.
BACKGROUND: We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model. METHODS:PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 105 cells/cm2 of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale. RESULTS: In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs. CONCLUSION: The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use. LEVEL OF EVIDENCE: n/a. TYPE OF STUDY: Basic science.
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