Spinal cord injury patients receiving BMMSC show improvements compared to control group

Posted on April 9, 2019 Written by nhriordan Leave a Comment

This 2013 study features a treatment group (who received bone marrow mesenchymal stem cells) and a control group (who did not receive cells). 20 patients were in the treatment group and 20 in the control group, for a total of 40 patients with spinal cord injuries. The MSCs were harvested from the bone marrow of the participants. Only mild adverse events (fever and headache) were reported in the treatment group. Patients who did not receive cells showed no improvement after 6 months. Half (10/20) of those who received bone marrow MSC showed improvements in motor or sensory function, or in ASIA grades (9/20). The differences in scores between those who did not receive cells and those who did receive BMMSC were statistically significant.

2013 Oct 2;1533:73-9. doi:10.1016/j.brainres.2013.08.016. Epub 2013 Aug 12.

Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R.

Abstract

Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.

PMID: 23948102

Early study (2008) of bone marrow stem cells for spinal cord injury

Posted on April 5, 2019 Written by nhriordan Leave a Comment

Research on the treatment of spinal cord injury with cells from bone marrow aspirate was already ongoing more than a decade ago. This 2008 study followed 8 patients for for 2 years after receiving an average of 90 million CD34 cells directly to the spinal cord with no serious adverse events. The patients reported improvements in scores using various scales (ASIA, Barthel, Frankel, Ashworth), and changes to the spinal cord were observed on MRI. The authors note that they continued on to safely treat 52 more patients. While the authors did not quantify the number of mesenchymal stem cells (MSCs) in the aspirate concentrate, this is one of the earlier studies that paved the way for current research with MSCs.

2008;17(12):1277-93. https://doi.org/10.3727/096368908787648074

Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies.

Geffner LF, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad AH, Montenegro X, Gonzalez R, Silva F.

Abstract

Presently, there is no cure or effective treatment for spinal cord injury (SCI). Studies in SCI patients have shown that for a treatment to be effective it must primarily improve their quality of life. Numerous studies have shown that stem cells represent an alternative treatment for various disorders and have shown promise in several disease/trauma states. For instance, the use of autologous CD34+ stem cells has been shown to ameliorate symptoms of several disorders such as leukemia, cardiomyopathy, diabetes, and several autoimmune diseases, including multiple sclerosis. For the first time, we report eight case studies of SCI (four acute, four chronic) with approximately 2 years of follow-up that were administered bone marrow stem cells (BMSCs) via multiple routes: directly into the spinal cord, directly into the spinal canal, and intravenous. Magnetic resonance imaging illustrated morphological changes in the spinal cord of some of the patients following BMSCs administration. Comprehensive evaluations demonstrate improvements in ASIA, Barthel (quality of life), Frankel, and Ashworth scoring. Moreover, in order to assess bladder function, we designed a simple numerical clinical scoring system that demonstrates significant changes in bladder function following BMSCs administration. To date, we have administration BMSCs into 52 patients with SCI and have had no tumor formations, no cases of infection or increased pain, and few instances of minor adverse events. These studies demonstrate that BMSCs administration via multiple routes is feasible, safe, and may improve the quality of life for patients living with SCI.

PMID: 19364066

Early treatment with BMMSC for spinal cord injury results in long-term benefits

Posted on March 18, 2019 Written by nhriordan Leave a Comment

The earlier, the better: in spinal cord injuries, treatment with mesenchymal stem cells may make a difference if applied soon after trauma. In this 2015 Polish case report, a 15 year old girl was treated with bone marrow MSC just 21 days after injury. She was paraplegic at the start of treatment (able to move her arms, but no control over trunk, legs, or bowels). She received 154 million BMMSC, spaced over every 3-4 months over the course of 2 years. At the end of treatment, the patient was able to stand, regained control over her trunk and sensation in her legs and bowels.

2015;24(4):661-72. doi: 10.3727/096368915X687796. Epub 2015 Mar 24.

Continuous improvement after multiple mesenchymal stem cell transplantations in a patient with complete spinal cord injury.

Jarocha D, Milczarek O, Wedrychowicz A, Kwiatkowski S, Majka M.

Abstract

Interruption of spinal cord (SC) continuity leads to functional loss below the lesion level. The purpose of this study was to evaluate the safety and efficacy of bone marrow nucleated cell (BMNC) and multiple mesenchymal stem cell (MSC) transplantations in spinal cord injury (SCI). A patient with total SC interruption at the Th2-3 level underwent experimental therapy with BMNC and MSC transplantations followed with intensive neurorehabilitation treatment. At admission, 6 h after SCI, the patient was scored ASIA A, had a Th1 sensation level, paraplegia with sphincter palsy, and was without the ability to control trunk movement. Neurophysiology examination showed bilateral axonal damage to the motor and sensory neural fibers with no motor unit potentials or peripheral motor nerve conduction in the lower extremities. The standard therapy had been applied and had not produced any positive results. The patient was treated with autologous BMNCs injected intravenously (3.2×10(9)) and intrathecally (0.5×10(9)) 10 weeks after the SCI and with five rounds of MSCs every 3-4 months (1.3-3.65×10(7)) administered via lumbar puncture. Total number of transplanted MSC cells during the course of treatment was 1.54×10(8). There were no complications related to transplantations and no side effects related to the therapy during 2 years of treatment. The ASIA score improved from A to C/D (from 112 to 231 points). The sensation level expanded from Th1 to L3-4, and the patient’s ability to control the body trunk was fully restored. Bladder filling sensation, bladder control, and anal sensation were also restored. Muscle strength in the left lower extremities improved from plegia to deep paresis (1 on the Lovett scale). The patient’s ability to move lower extremities against gravity supported by the movements in quadriceps was restored. The patient gained the ability to stand in a standing frame and was able to walk with the support of hip and knee ortheses. Magnetic resonance imaging (MRI) revealed that at the Th2/Th3 level, where the hemorrhagic necrosis was initially observed, small tissue structures appeared. Our results suggest that repeated intrathecal infusions of MSCs might have the potential to produce clinically meaningful improvements for SCI patients.

PMID: 25807231

Repeated doses of bone marrow MSCs bring nerve pain relief in spinal cord injury patients

Posted on March 6, 2019 Written by nhriordan Leave a Comment

Neuropathic pain, also known as nerve pain or neuralgia, occurs when there is damage to the nerves; it is one of the major consequences of spinal cord injury. In this study based in Spain, 10 patients received a dose of 100 million bone marrow MSCs, repeated at 4 months and 7 months. No adverse events were reported during the 10-month follow-up period. 9 out of 10 of patients reported relief in neuropathic pain. Their mean pain scores significantly decreased from 5.50 to 1.50, as measured by standard pain scales. This shows that MSC therapy (particularly in repeated doses) is a safe and potentially beneficial treatment option for spinal cord injury patients suffering from neuralgia.

2018 Mar 23;670:14-18. doi: 10.1016/j.neulet.2018.01.035. Epub 2018 Feb 2.

Intrathecal administration of autologous bone marrow stromal cells improves neuropathic pain in patients with spinal cord injury.

Vaquero J, Zurita M, Rico MA, Aguayo C, Fernández C, Gutiérrez R, Rodríguez-Boto G, Saab A, Hassan R, Ortega C.

Abstract

Neuropathic pain (NP) is highly disabling, responds poorly to pharmacological treatment, and represents a significant cause of decreased quality of life in patients suffering from spinal cord injury (SCI). In recent years, cell therapy with autologous mesenchymal stromal cells (MSCs) has been considered as a potential therapeutic weapon in this entity. Ten patients suffering chronic SCI received 100 million MSCs into subarachnoid space by lumbar puncture (month 1 of the study) and this procedure was repeated at months 4 and 7 until reaching a total doses of 300 million MSCs. Intensity of NP was measured by standard numerical rating scale (VAS) from 0 to 10, recording scores previous to the first MSCs administration and monthly, until month 10 of follow-up. Months 1, 4, 7 and 10 of the study were selected as time points in order to a statistical analysis by the nonparametric Wilcoxon rank test. Our results showed significant and progressive improvement in NP intensity after the first administration of MSCs (p: 0.003). This study supports the benefit of intrathecal administration of autologous MSCs for the treatment of NP in patients with SCI.

PMID: 29366770

Human CD34 improves locomotor function in spinal cord injury rats

Posted on March 18, 2016 Written by nhriordan Leave a Comment

In this new 2016 study, rats with spinal cord injury (SCI) were treated with conditioned medium or secretome obtained from human CD34 umbilical cord stem cells. Locomotor function was improved; in particular, neurological deficits, cell death, extent of inflammation, oxidative stress and astrogliosis were attenuated.

These findings corroborate our results published in 2010 – a spinal cord injury patient reported decreases in neuropathic pain and ASIA scores, recovery of muscle, bowel and sexual function, following treatment with umbilical cord CD34 and stem cells.

Taiwan J Obstet Gynecol. 2016 Feb;55(1):85-93. doi: 10.1016/j.tjog.2015.12.009.

Attenuating spinal cord injury by conditioned medium from human umbilical cord blood-derived CD34(+) cells in rats.

Yeng CH, Chen PJ, Chang HK, Lo WY, Wu CC, Chang CY, Chou CH, Chen SH.

Abstract

OBJECTIVE:

Intravenous or intraspinal transplantation of human umbilical cord blood cells-derived CD34(+) cells (human CD34(+) cells) or mesenchymal stem cells after spinal cord injury (SCI) improved hind limb functional recovery in adult rats. The objective of this study is to ascertain whether SCI in rats can be attenuated by conditioned medium (CM) or secretome obtained from cultured human CD34(+) stem cells.

MATERIALS AND METHODS:

Sprague-Dawley rats were assigned to one of the following five groups: the sham group, the SCI group treated with vehicle solution (SCI + V), the SCI group treated with CM (SCI + CM), the SCI group treated with 17β-estradiol E2 (10 μg; SCI + E2), and the SCI group treated with CM plus E2 (SCI + CM + E2). A 0.5-mL volume of CM or vehicle solution was administered intravenously immediately after SCI.

RESULTS:

Compared with the sham group, the (SCI + V) group had significantly higher scores of neurological motor dysfunction as well as inflammation apoptosis, oxidative stress, and astrogliosis in the injured spinal cord. The neurological deficits, numbers of apoptotic cell, extent of inflammation, oxidative stress, and astrogliosis in the injured spinal cord were significantly attenuated by CM, E2, or CM plus E2, but not by the vehicle solution. In addition, the neuroprotective effect exerted by a combination of CM and E2 is superior to that exerted by CM- or E2-alone therapy.

CONCLUSION:

The neuroprotective effects of CM from cultured human CD34(+) cells are similar to those of human CD34(+) cells and the CM was found to enhance the neuroprotective effects of E2 in rat SCI.

Copyright © 2016. Published by Elsevier B.V.

PMID: 26927256