UC-MSCs Are Explored For Treatment of Spine Conditions

Spinal cord
In Brief: Bone marrow MSCs, adipose tissue MSCs, umbilical cord MSCs and mononuclear cells have long been used in transplantations for a wide array of treatments. Umbilical cord blood and cord tissue-derived mesenchymal stem cells (UC-MSCs) are undergoing several clinical trial phases to test the safety and efficacy for use in infusions for patients with low back pain (LBP), intervertebral disc degeneration (IVD), and spinal cord injury (SCI).
 

Lower Back Pain Breakdown

  • 80% of the population is affected by lower back pain during their lifetime.1
  • Affects joint mobility and posture
  • Affects men and women equally alike

About Lower Back Pain

The exact cause of low back pain (LBP) is unknown; however, several factors such as age, obesity, smoking, genetics, bacterial infection, and mechanical loading can attribute to its existence. Moreover, degeneration of the intervertebral disc is believed to be the primary catalyst of LBP.2 Lower back pain can present clinically in varying degrees from acute, that is less than six weeks; sub-acute, six to twelve weeks; and chronic, more than twelve weeks. Patients exhibiting chronic back pain experience pain-free periods, followed by the occurrence of episodic pain and disability with worsening degrees of lumbar modality.

Tissue Engineering

Through the manipulation of living cells, biological substitutes for transplantation are able to foster the remodeling, repairing, and enhancing of tissue and organ functionality.3 Cord blood and cord tissue are an appealing source of stem cells for regenerative medicine and cellular therapies because of their anti-inflammatory, differentiating, and immunity properties. A tissue engineering approach with the use of cells combined with a biomaterial scaffold, to regenerate the matrix while restoring disc height, remains an attractive strategy to treating LBP.4 A damaged disc has a limited capacity for self-repair. At the cellular level, the degeneration process is characterized by cellular dysfunction accompanied by reduced synthesis of extracellular matrix (ECM).4

Therapeutic interventions can aid in pain management, but do not, currently, reverse the process of disc degeneration. Recent research points to the fact that MSCs have the ability to differentiate into osteo-chondrocyte lineages. Several animal and human clinical trial studies have shown positive outcomes with the use of MSCs from various sources in low back pain therapies. Dr. Xiaodong Pang and colleagues at the Department of Spinal Surgery of Armed Police Force General Hospital in Beijing conducted a preliminary study to test the safety and efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) to treat chronic discogenic low back pain.

Study Outcomes

The case study was the first to involve UC-MSCs rather than bone marrow MSCs in the treatment of patients with chronic discogenic low back pain. It should be noted, the scope of the study was limited to two patients, but clinical outcomes demonstrated that pain and function notably improved during the course of a two year follow-up.5

Case 1: Female patient exhibited a limited range of flexion, extension, and lateral bending with tenderness over the L4-L5 lumbar spine. Her lumbar MRI scan showed L3/4, L4/5, and L5/S1 disc degeneration without disc herniation.L3/4 and L5/SI discs showed grade 5 disruption, according to the Modified Dallas Discogram Description. Pain and improved lumbar function were evaluated using the 11-point Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI).  

Case 1 Results: The VAS score was 7 before UC-MSC transplantation, with a VAS score of 2, 1, and 1 at 6, 12, and 24 months, respectively, after transplantation. 

The ODI was 46 before UC-MSC transplantation, and was 10, 5, and 5 at 6, 12, and 24 months, respectively, after transplantation.

Case 2: Male patient’s lumbar MRI revealed L3/4 disc degeneration and no signs of disc herniation. The discography revealed L3/4 disc grade 5 disruption with pain reproduction.

Case 2 Results: VAS scores improved from 8 before transplantation to 2, 3, and 4, respectively, at 6, 12, and 24 months after the procedure.

ODI scores decreased from 56 before transplantation to 10, 15, and 20, respectively, at 6, 12, and 24 months after the procedure.

In both cases, the patients experienced alleviated pain, and in the case of patient one, the presence of elevated water content in the degenerative disc was found. Research has determined disc hydration correlates with load capability.6 Clinical trial studies involving a larger sample size need to be conducted to prove the consistency of results. Still, these outcomes are promising, coupled with the findings of animal studies specifically targeting UC-MSCs.

About Spinal Cord Injury (SCI)

In a similar vein, many people in the United States suffer from spinal cord injury, with a reported 17, 810 new cases each year. The estimated number of people with SCI living in the U.S. is approximately 291,000 people.6 Remarkable work is being conducted by Dr. Wise Young and his colleagues at W.M. Keck Center for Collaborative Neuroscience. Young and his team have conducted numerous studies involving animal models that show spontaneous regeneration in the spinal cord. Through umbilical cord transfusion, axons were able to cross over the injury site and allow regeneration to occur, allowing the ability for walking to occur.

Study Outcomes

With this discovery, Dr. Young and colleagues continued animal trials testing the safety and dosage of cord blood stem cells in animal models. Studies showed that rats, mice, and dogs with umbilical cord blood mononuclear cells started walking. These studies led to Phase I and Phase II clinical trials of 8 patients in Hong Kong and another involving 20 patients in Kunming. It was observed that higher cord blood stem cell dosage equated to better patient walking outcomes. In fact, 75% of patients were walking with assistance after the one-year follow-up, and 65% of patients recovered bowel and bladder function. Even more surprising is that lithium, a drug used for manic depression, was responsible for producing more axonal growth, which formed a bridge over the injury site.7

Hong Kong Trial

All eight patients had “complete” injury as indicated by The American Spinal Injury Association Impairment Scale (ASIA) with a walking score of 0, as indicated by The Walking Index for Spinal Cord Injury (WISCI).

The trial shows that 4–8 microliters (μl) of umbilical cord blood mononuclear cells could be safely injected into the spinal cord above and below the injury site. Magnetic resonance diffusion tensor images suggest that white matter gaps decreased at the injury site, and two patients showed bundles of fibers growing across the injury site into surrounding spinal cord at 6–18 months.7

Kumming Trial

19 out of 20 patients were classified as AISA with C5-T11 neurological levels. With the exception of two patients who had a WISCI score of two, all patients had a walking index score of 0.

The trial shows that 4, 8, and 16 μl of umbilical cord blood mononuclear cells can be safely injected into the spinal cord. Over half of the patients recovered walking with minimal or no assistance by 6–12 months after umbilical cord blood mononuclear cell administration and locomotor training, as well as increased independence in activities of daily living, including self-care, bowel and bladder management, and mobility.7

Due to these results, the FDA approved a Phase III clinical trial to take place this year. It will be the first clinical trial directed for patients of complete spinal cord injury. There will be three groups of patients: 1 group will receive 6/6/6 walking training—meaning, walking six hours/day, six times a week, for a six-month duration; 1 group will receive cord blood stem cells in addition to 6/6/6 training; 1 group will receive cord blood stem cells, with lithium, and 6/6/6/ training.8 Those participating in this trial will be 18-64 years of age. However, there are also plans for another clinical trial involving children ages 8-17, and one which will include patients 65-80 years of age.

Sources:
1. National Institute of Neurological Disorders and Stroke. Back Pain Fact Sheet. NINDS (2014, December) Retrieved August 2, 2019, from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Low-Back-Pain-Fact-Sheet

2. Rannou F, Lee TS, Zhou RH, et al. Intervertebral disc degeneration: the role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload. Am J Pathol. 2004;164(3):915–924. doi:10.1016/S0002-9440(10)63179-3

3. Steck, Eric, Betram, Helge, Abel, Rainer, Chen, Bohua, Winter, Anja, Ritcher, Wiltrud Dr. Induction of Intervertebral Disc-Like Cells From Adult Mesenchymal Stem Cells. Stem Cells Journal. Retrieved August 2, 2019, from https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1634/stemcells.2004-0107

4. Vickers, Louise, Thorpe. A Abbey, Snuggs, Joseph, Sammon, Christopher, Le Maitre L. Christine. Mesenchymal stem cell therapies for intervertebral disc degeneration: Consideration of the degeneration niche. Wiley Online Library. Retrieved August 2, 2019, from https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1055

5. Pang, Xiaodong, MD, PhD, Yang, Hong, MD, Peng, Baogan, MD, PhD. Human Umbilical Cord Mesenchymal Stem Cell Transplantation for the Treatment of Chronic Discogenic Low Back Pain. Pain Physician 2014; 17:E525-E530. Retrieved August 2, 2019, from https://pdfs.semanticscholar.org/fc83/e2848cd14f4a553d497af018c215fcacf164.pdf

6. https://www.nscisc.uab.edu/Public/Facts%20and%20Figures%202019%20-%20Final.pdf

7. Zhu, H., Poon, W., Liu, Y., Leung, G. K.-K., Wong, Y., Feng, Y., … Young, W. (2016). Phase I–II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury. Cell Transplantation, 25(11), 1925–1943. doi: 10.3727/096368916x691411

8. https://clinicaltrials.gov/ct2/show/NCT01471613?term=spinal+cord+injury%2C+cord+blood&draw=2&rank=1

 

Last Updated on: 08/13/2020 by Amy Schmidt