CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissueederived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome

“…This safety profile is consistent with the experience of other human clinical trials involving MSC therapy. 33,[37][38][39][40][41][42][43] The potential efficacy of MSC therapy for ARDS in COVID- Findings from this study also suggest the impact of MSC therapy on important immunologic and inflammatory processes that lead to organ injury in COVID-19-infected patients. Cytokine release syndrome is a major underlying pathophysiological process in ARDS and was found to decrease with MSC therapy in seven of the studies analyzed.…”

“…These showed clear decreases in pro-inflammatory cytokines, including IL-1, IL-6, TNF-α, and CRP, and increased lymphocytes and IL-10 within 5 days of MSC therapy (Table 5), [20][21][22]24,25,28 which supported an immunomodulatory effect of the MSC therapy. clinical studies have demonstrated that MSC therapy is safe and has the potential to mitigate inflammatory and physiologic damage for a variety of conditions involving the central nervous, 32,33 cardiac, 34,35 renal, 36 gastrointestinal, [37][38][39] and respiratory 40,41 systems. Our analysis of the literature suggests similar results for MSC therapy for treating ARDS in COVID-19 patients.…”

The Effect of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells’ Therapy in the Treatment of Chronic Posttraumatic Spinal Cord Injury in a Domestic Ferret Patient

“…Despite promising results obtained with preclinical studies, there are still very few reports in the available literature describing successful application of ADSCs for SCI treatment in clinical trials. However, Bydon et al 26 published the outcomes obtained with an ongoing phase 1 clinical trial conducted at Mayo Clinic ( ClinicalTrials.gov Identifier: NCT03308565) 27 . The mentioned case report describes the ADSC-based therapy of paralysis after traumatic SCI.…”

Treatment of spinal cord injury with mesenchymal stem cells

“…However, MRI examination indicated that the lesion size remained unchanged. In a recent paper, Bydon et al [ 65 ] reported the treatment of a SCI patient with 100 million autologous ADSCs. The cells were administered intrathecally.…”