Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study
Introduction
Spinal cord injury (SCI) is a severe neurological disorder that may result in functional deficit and clinical dependency due to paralysis [1]. Despite several advancements, the currently available treatment strategies, such as pharmacological intervention, surgical management and rehabilitation techniques, provide limited results [2]. Cellular transplantation has recently immerged as a possible therapeutic approach to SCI [3]. For this purpose, various cell types have been used in preclinical and limited clinical trials; these include Schwann cells, macrophages, olfactory ensheathing cells and adult stem cells, such as neural stem cells, umbilical cord blood stem cells, mesenchymal stromal cells (MSCs) and induced pluripotent stem cells [4], [5], [6], [7], [8], [9].
MSCs are attractive candidates for cellular transplantation strategies. MSCs are found in many adult and fetal tissues. They can be easily obtained from a variety of tissue sources, expanded in long-term cultures without cytogenetic changes, and potentially differentiate into various lineages including neural cells, both in vitro and in vivo upon induction. MSC transplantation in experimental models of SCI resulted in functional recovery by increasing area of tissue sparing, remyelination of spared white matter and enhanced axonal regeneration [10]. According to recent work, MSCs accomplish therapeutic effect primarily by secretion of neurotrophic factors and provision of stromal support to augment repair at site of spinal injury [11]. We present here a pilot study on the safety of autologous transplantation of ex vivo expanded autologous BM-MSCs in a Pakistani cohort of spinal cord injury patients.
Section snippets
Selection of patients
This pilot study was designed to determine the safety and feasibility of autologous transplantation of MSCs in spinal cord injury patients. The study was approved by institutional review boards and ethical committees of both participating hospitals under guidelines of Pakistan Medical Research Council (PMRC) and registered at clinicaltrials.gov (NCT02482194). Nine patients suffering from sub-acute or chronic traumatic spinal cord injury of thoracic level were included in the study. All patients
Subjects
During this pilot study, nine male patients underwent transplantation of autologous marrow-derived cultured MSCs. All patients had complete spinal transection of thoracic segment (between T3 and T12) and ASIA impairment score A. Group 1 included 6 patients having chronic spinal cord injury with median time from injury 33 months (range: 10–55 months). The remaining three patients had sub-acute injury and constituted group 2. Patient demographics and disease characteristics are shown in Table I.
MSC characterization
Discussion
SCI is a devastating neurological disorder that leads to disability and debilitation. Although vigorous research in recent years has increased our understanding of the molecular events that follow the spinal injury, its cure has been elusive, and current treatment strategies have met little success. Treatment options in SCI include biological, surgical and pharmacological approaches [13]. During the past decade, many preclinical experiments and limited clinical trials have demonstrated
Acknowledgments
We thank the doctors and rehabilitation support staff for their special attention to these patients during their extended stay at the hospital.
This study is registered with clinicaltrials.gov (NCT02482194).
Disclosure of interest: The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.
References (18)
- et al.
Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy
Mol Ther
(2004) - et al.
The bright side of the glial scar in CNS repair
Nat Rev Neurosci
(2009) Steroids for acute spinal cord injury
Cochrane Database Syst Rev
(2012)- et al.
Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor
Tissue Eng
(2005) - et al.
Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: survival, migration, axon association, and functional recovery
Glia
(2007) - et al.
Peripheral olfactory ensheathing cells reduce scar and cavity formation and promote regeneration after spinal cord injury
J Comp Neurol
(2004) - et al.
Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats
J Neurosci Res
(2002) - et al.
Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis
J Biomed Biotechnol
(2012) - et al.
Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors
PLoS ONE
(2015)
Cited by (109)
Macromolecule-based hydrogels nanoarchitectonics with mesenchymal stem cells for regenerative medicine: A review
2023, International Journal of Biological MacromoleculesYoga as a therapeutic intervention for the management of neurodegenerative disorders
2023, Ayurvedic Herbal Preparations in Neurological DisordersMultiple strategies enhance the efficacy of MSCs transplantation for spinal cord injury
2023, Biomedicine and PharmacotherapyTransplantation of IGF-1-induced BMSC-derived NPCs promotes tissue repair and motor recovery in a rat spinal cord injury model
2022, HeliyonCitation Excerpt :Recently, a study has shown that intrathecal transplantation of allogeneic BMSCs did not produce neurological deficits or immune rejection against donor cells in a canine model (Benavides et al., 2021). Similarly, studies have reported that both autologous and allogeneic BMSCs can be safely administered in SCI patients (Pan et al., 2019; Karamouzian et al., 2012; Vaquero et al., 2017; Satti et al., 2016). All these pieces of evidence suggest that BMSCs could be a potential therapy for irreversible damage to the CNS.