Minimally manipulated autologous adherent bone marrow cells (ABMCs): a promising cell therapy of spinal cord injury

Minimally manipulated autologous adherent bone marrow cells (ABMCs): a promising cell therapy of spinal cord injury

Spinal cord injury (SCI) is a devastating ailment that results in drastic life style alterations for the patients and their family members (McDonald and Sadowsky, 2002). Damage post injury causes necrosis, edema, hemorrhage and vasospasm. Post injury, secondary damage is caused by ischemia, excitotoxicity, lipid peroxidation, free radicals production, and inflammation. Collectively, damage to multiple neuronal and glia sub-types leads to severed axonal connections, demyelination and scar tissue formation. Interventions therefore require regeneration of multiple axonal projections to recreate the lost neuronal diversity originally achieved through an elaborate, tightly regulated transcriptional code during development. Neuronal repair and regeneration post injury is impeded due to absence of such supportive environment in the adult spinal cord (Misra et al., 2014).

Impressive research advances using cell therapies have ushered in an era of new hope and today we are witnessing the translation of studies utilizing mesenchymal stem cells (MSCs) into mainline therapies for patients with SCIs. A testimonial to this trend is the surge in clinical studies using cellular transplantation for SCI (Tetzlaff et al., 2011). A search within (clinical trail.gov) using "MSCs transplantation" as search terms yielded ~400 studies, with only 6% of them related to SCI repair. Studies at EU clinical trial registry follow similar trends. Within the SCI domain, the majority of studies (69%) utilize BM-derived cells, followed by adipose tissue-derived MSCs (23%) and umbilical cord-derived cells ([Figure 1]a). While exciting at a first glance, a deeper analysis only highlights the confusion that prevails in the field of adult stem cells. The types of cells used and standards for study design and reporting are far from being well defined, despite organized efforts (Steeves et al., 2007). Given the variability in cell derivation protocols, it is extremely difficult to draw valid conclusions from these different (MSCs) cell therapy studies. Additionally, beyond the registered studies, there is alarming number of studies and treatments that are carried out without any controls or standards for safety and outcome measures, creating wrong perceptions in the public outlook. In this perspective, we have extrapolated the documented studies of cellular therapy for SCI to objectively draw inferences on the mechanisms of injury repair, and provide an outlook for bone marrow (BM)-derived cell therapy in the context of SCI.

Spinal cord injury (SCI) is a devastating ailment that results in drastic life style alterations for the patients and their family members (McDonald and Sadowsky, 2002). Damage post injury causes necrosis, edema, hemorrhage and vasospasm. Post injury, secondary damage is caused by ischemia, excitotoxicity, lipid peroxidation, free radicals production, and inflammation. Collectively, damage to multiple neuronal and glia sub-types leads to severed axonal connections, demyelination and scar tissue formation. Interventions therefore require regeneration of multiple axonal projections to recreate the lost neuronal diversity originally achieved through an elaborate, tightly regulated transcriptional code during development. Neuronal repair and regeneration post injury is impeded due to absence of such supportive environment in the adult spinal cord (Misra et al., 2014).

Impressive research advances using cell therapies have ushered in an era of new hope and today we are witnessing the translation of studies utilizing mesenchymal stem cells (MSCs) into mainline therapies for patients with SCIs. A testimonial to this trend is the surge in clinical studies using cellular transplantation for SCI (Tetzlaff et al., 2011). A search within (clinical trail.gov) using "MSCs transplantation" as search terms yielded ~400 studies, with only 6% of them related to SCI repair. Studies at EU clinical trial registry follow similar trends. Within the SCI domain, the majority of studies (69%) utilize BM-derived cells, followed by adipose tissue-derived MSCs (23%) and umbilical cord-derived cells ([Figure 1]a). While exciting at a first glance, a deeper analysis only highlights the confusion that prevails in the field of adult stem cells. The types of cells used and standards for study design and reporting are far from being well defined, despite organized efforts (Steeves et al., 2007). Given the variability in cell derivation protocols, it is extremely difficult to draw valid conclusions from these different (MSCs) cell therapy studies. Additionally, beyond the registered studies, there is alarming number of studies and treatments that are carried out without any controls or standards for safety and outcome measures, creating wrong perceptions in the public outlook. In this perspective, we have extrapolated the documented studies of cellular therapy for SCI to objectively draw inferences on the mechanisms of injury repair, and provide an outlook for bone marrow (BM)-derived cell therapy in the context of SCI.

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