Administration of Adipose-Derived Mesenchymal Stem Cells via Intrathecal Injection for Traumatic Spinal Cord Injury

by admin | Jan 3, 2025 | Adipose, Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy

With over 290,000 people in the United States living with SCI and with roughly 17,000 new cases each year, spinal cord injury (SCI) is a serious condition that significantly impacts the lives of those affected. 

Considering the complexity associated with SCI, current treatments for SCI continue to focus mainly on managing symptoms and providing physical rehabilitation. However, recently there has been growing interest in exploring the potential of regenerative medicine, particularly stem cell therapy, for treatment of SCI.

Bydon et al.’s Phase I clinical trial explored the safety of injecting autologous adipose-derived mesenchymal stem cells (AD-MSCs) into the spinal fluid of patients with traumatic spinal cord injury (SCI). 

The study successfully manufactured and administered the stem cells to all patients without any serious adverse events (AEs). Although some non-serious AEs, including headache and musculoskeletal pain, were observed, none of the patients were excluded from the study as a result. 

At the conclusion of this study, the authors found that several participants showed improvements in sensory and motor functions, as assessed by the American Spinal Injury Association (AIS) impairment scale.

Previous research has indicated that mesenchymal stem cells (MSCs) might aid in neurogenesis, angiogenesis, immune regulation, and neuronal plasticity. AD-MSCs, in particular, are advantageous due to their ability to regenerate nerves and blood vessels, their ease of extraction, and availability. 

This study’s findings align with earlier studies, which also reported no serious AEs from intrathecal AD-MSC injections in SCI patients. Similar safety profiles were observed in studies involving other neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and multiple sclerosis.

Bydon et al.’s reported changes in MRI scans following the stem cell injections as part of this study. Previous studies have reported mixed conclusions on whether these changes are linked to neurological decline. Some suggest that these MRI findings could be due to inflammation from the stem cell treatment, potentially leading to nerve root compression. However, in this study, the authors found that these MRI changes did not correlate with neurological deterioration, indicating that they might be benign reactions.

While some patients showed improvements in their AIS grades, the authors caution that these findings should be carefully interpreted due to the limitations associated with this Phase I trial, including the lack of a control group. 

Bydon et al. call for future larger-scale, randomized controlled trials to conclusively determine the benefits of AD-MSC injections. Additionally, they recommend expanding the study to include a broader range of cytokines and immunomodulatory markers to provide a deeper understanding of the stem cells’ mechanisms.

The authors conclude that this trial demonstrated the safety of intrathecal AD-MSC injections in SCI patients, with no serious AEs reported. Seven out of ten patients showed improvements in their AIS grades. These results encourage further research to evaluate the impact of AD-MSCs on neurological outcomes and to explore their potential in aiding late-stage recovery in SCI patients.

Source: Bydon M, Qu W, Moinuddin FM, Hunt CL, Garlanger KL, Reeves RK, Windebank AJ, Zhao KD, Jarrah R, Trammell BC, El Sammak S, Michalopoulos GD, Katsos K, Graepel SP, Seidel-Miller KL, Beck LA, Laughlin RS, Dietz AB. Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial. Nat Commun. 2024 Apr 1;15(1):2201. doi: 10.1038/s41467-024-46259-y. Erratum in: Nat Commun. 2024 Jun 5;15(1):4799. doi: 10.1038/s41467-024-48979-7. PMID: 38561341; PMCID: PMC10984970.

Phase 1 Clinical Trial Investigating the Use of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Traumatic Spinal Cord Injury

by admin | Feb 22, 2024 | Spinal Cord Injury, Adipose, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy

With more than 17,000 people in the US sustaining a spinal cord injury (SCI) each year and an estimated combined cost to healthcare and the workforce exceeding $40 billion, the condition has significant personal and socioeconomic implications. In addition, SCIs have limited pharmacological treatment options to support the regeneration of nerve damage.

Considering the limited treatment options for this condition, the field of regenerative medicine, and specifically the use of stem cells, has recently drawn interest as a potential therapeutic treatment option for paralysis resulting from SCIs.

In this report, Bydon et al. summarize findings of the ongoing multidisciplinary phase 1 clinical trial exploring the safety and efficacy of intrathecal autologous adipose tissue-derived (AD) mesenchymal stem cells (MSCs) in patients with blunt, traumatic SCI.

Specifically, as part of this report, the authors describe the outcome of the first patient with C3-4 SCI treated with AD-MSCs. At the time of SCI, neurologic examination revealed complete loss of motor and sensory function below the level of injury; an injury diagnosed as an American Spinal Injury Association (ASIA) grade A SCI. 

After undergoing initial treatment, including C2-6 posterior cervical decompression and fusion, improvement in motor and sensory function was demonstrable. However, neurological gains plateaued 6 months after sustaining injury.

Upon enrollment into the CELLTOP clinical trial 9 months after injury, the patient’s neurologic status was found to be ASIA grade C and imaging revealed bilateral myelomalacia at the C3 level and at the C2-6 decompression and fusion. Additionally, an open biopsy of adipose tissue found in the abdominal wall was performed 8 weeks prior to receiving an initial intrathecal injection. 

After receiving an intrathecal injection of 100 million autologous AD-MSCs 11 months after injury, the patient was observed for clinical signs of efficacy at 3, 6, 12, and 18 months following injection.

Bydon et al. observed progressive improvement in upper extremity motor scores and considerable improvement in lower extremity scores at 18 months following injection. The patient also demonstrated consistent improvement in ASIA sensory score, including improvements in pinprick and light touch scores at follow-up after 18 months. The authors reported patient improvements in Capabilities of Upper Extremity score, quality of life (as measured by Global Health Score), and in physical and occupational therapy measures. Other than a moderate headache on day 2, no other safety issues or adverse events were reported. 

While further clinical trial is required, the authors conclude that intrathecal AD-MSC administration may be a relatively noninvasive and safe therapeutic option for patients with SCI to improve their neurologic status after reaching a ceiling effect in terms of spontaneous recovery.

Source: “First Report From a Phase 1 Trial of Autologous Adipose Tissue ….” 27 Nov. 2019, https://www.mayoclinicproceedings.org/article/S0025-6196(19)30871-7/fulltext.