Mult Scler J Exp Transl Clin. 2018 Mar 26;4(1):2055217318765288. doi: 10.1177/2055217318765288. eCollection 2018 Jan-Mar.

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

Planchon SM¹, Lingas KT², Reese Koç J², Hooper BM², Maitra B², Fox RM², Imrey PB^1,3, Drake KM⁴, Aldred MA⁴, Lazarus HM², Cohen JA¹.

Abstract

Background:

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited.

Objective:

To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use.

Methods:

In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10⁶ cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls.

Results:

One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture.

Conclusion:

Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.