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

Abstract

BackgroundMultiple 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.ObjectiveTo determine the feasibility of culture-expanding multiple sclerosis patients’ mesenchymal stem cells for clinical use.MethodsIn 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.ResultsOne 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.ConclusionCulture 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.

Mesenchymal stem cells: Cell therapy and regeneration potential

“…Stem cell‐based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, ; Han et al, ; J. Shin et al, ; X. Wang, Ma, et al, ), DDD (Ahn et al, ; Beeravolu et al, ; Pereira et al, ; Perez‐Cruet et al, ), MS (Harris et al, ; Nasri et al, ; Planchon et al, ), PD (Jamali et al, ; H. Kim, Lee, et al, ), and RDD (Mead, Amaral, & Tomarev, ), as summarized in Table . The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ).…”

“…These dopaminergic neuron cells survived when transplanted into a rat model of PD and displayed greater improvement of behavioral impairments (Y. Wang et al, ). In addition, MSCs have been investigated for the treatment of MS (Harris et al, ; Nasri et al, ; Planchon et al, ). Potential of the MSCs differentiated into neural progenitor cells was investigated to treat MS using a chronic experimental autoimmune encephalomyelitis (EAE) mouse model (Constantinescu, Farooqi, O'Brien, & Gran, ).…”

“…In another similar study, MSCs injected intradiscally into the IVD of the patients resulted in a quick and significant improvement in functionality and in patients experiencing less pain and exhibited less IVD degeneration than the control group (Noriega et al, ). Additionally, a Phase 1 study showed promising therapeutic effects of MSCs for the treatment of MS (Harris et al, ; Planchon et al, ). When MSC‐derived neural progenitor cells were administered intrathecally in three separate doses in the span of 3 months, improvements in muscle strength and functional motor skills were observed (Harris et al, ).…”

“…MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, 2017;Han et al, 2018;X. Wang, Ma, et al, 2018), DDD (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018), MS (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018), PD (Jamali et al, 2018;H. Kim, Lee, et al, 2018), and RDD (Mead, Amaral, & Tomarev, 2018), as summarized in Table 2.…”

“…Wang, Ma, et al, 2018) Bone and cartilage diseases (Jo et al, 2014;Kastrinaki et al, 2013) Autoimmune diseases (Xu, 2018;W. Zhang, Feng, et al, 2018) Amyotrophic lateral sclerosis (Bonafede & Mariotti, 2017) Diabetes (Evangelista et al, 2018;Gabr et al, 2018) Glaucoma (Manuguerra-Gagne et al, 2013;Osborne, Sanderson, & Martin, 2018;Roubeix et al, 2015) Graft vs host disease (Jurado et al, 2017;Zhao et al, 2015) Intervertebral disc disease (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018) Multiple sclerosis (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018) Myocardial infarction ( investigated for the treatment of chronic tissue ulcers caused by diabetes. Patients were administered with MSCs for skin healing showed an improvement in microvascularisation structure (Kirana et al, 2012).…”