Case Report Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2022; 14(4): 303-309
Published online Apr 26, 2022. doi: 10.4252/wjsc.v14.i4.303
Treatment of syringomyelia using uncultured umbilical cord mesenchymal stem cells: A case report and review of literature
Hyunjun Ahn, Sang Yeon Lee, Kye-Ho Lee, Stem Cell Treatment and Research Institute (STRI), bio Beauty and Health Company (bBHC), Seoul 04420, South Korea
Won-Ju Jung, Stem Cell Treatment, 97.7 Beauty and Health Clinic, Seoul 04420, South Korea
ORCID number: Hyunjun Ahn (0000-0002-5550-8325); Sang Yeon Lee (0000-0003-4394-6958); Won-Ju Jung (0000-0002-4966-3118); Kye-Ho Lee (0000-0001-8241-6402).
Author contributions: Ahn H, Lee SY, Jung WJ, and Lee KH designed the report; Ahn H and Jung WJ collected the patient’s clinical data; Ahn H, Lee SY, and Jung WJ analyzed the data; Ahn H wrote the manuscript; Lee KH provided professional advice and revised the manuscript; All authors issued final approval for the version to be submitted.
Informed consent statement: The patient involved in this study gave her written informed consent authorizing disclosure of her protected health information.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kye-Ho Lee, PhD, Stem Cell Treatment and Research Institute (STRI), bio Beauty and Health Company (bBHC), No. 72 UN Village-gil, Yongsan-gu, Seoul 04420, South Korea. khlee@stc365.com
Received: December 13, 2021
Peer-review started: December 13, 2021
First decision: January 30, 2022
Revised: February 28, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: April 26, 2022

Abstract
BACKGROUND

Syringomyelia is a disease caused by the formation of a cavity inside the spinal cord and is accompanied by such symptoms as pain, paresthesia, and urination and defecation disorders, and in severe cases causes various paralyses. Currently, there are only surgical methods for the treatment of syringomyelia, but these methods carry the possibility of failure, recurrence, and side effects.

CASE SUMMARY

The patient was a 59-year-old woman who suffered from pain due to syringomyelia. For treatment, the patient received transplant of uncultured umbilical cord-derived mesenchymal stem cells. As intended, the patient's pain was relieved after treatment. Interestingly, an additional benefit was found in that the size of the cavity also decreased. After 2 years from the last treatment, the patient's cavity had almost completely disappeared and her syringomyelia was deemed cured.

CONCLUSION

Using uncultured umbilical cord-derived mesenchymal stem cells may be a new treatment alternative for syringomyelia.

Key Words: Syringomyelia, Umbilical cord mesenchymal stem cells, Cell therapy, Allogenic stem cells, Chiari malformations, Case report

Core Tip: Syringomyelia has no suitable treatment other than surgical methods, but these methods carry the possibility of failure, recurrence, and side effects. In this study, we treated a patient with syringomyelia using uncultured umbilical cord-derived mesenchymal stem cells. This method could be a new treatment alternative for syringomyelia.



INTRODUCTION

Syringomyelia is a disease in which a cavity composed of fluid similar to cerebrospinal fluid or extracellular fluid is formed inside the spinal cord and gradually expands, thereby damaging the spinal nerves[1-4]. Cerebrospinal fluid is a bodily fluid that surrounds the brain and spinal cord and is known to protect the brain and spinal cord from external shocks and to transport nutrients and waste products[5]. Cerebrospinal fluid is produced in the choroid plexus of the ventricles located inside the brain and circulates in the subarachnoid space around the brain and spinal cord[6]. It is known that a spinal cavity is formed when the circulation of the cerebrospinal fluid is blocked in the subarachnoid space[1-4].

Various diseases can cause syringomyelia to include Chiari malformation, arachnoiditis, scoliosis, spinal tumors, spina bifida, and the like[4,7]. It is also known that syringomyelia can occur in patients with spinal cord injury due to trauma[4,8]. The most common sites for syringomyelia are the cervical and thoracic portions of the spinal cord, and sometimes even the medulla oblongata[1-4]. Symptoms caused by syringomyelia vary, depending on the scope. Patients may experience pain, abnormal sensations, and loss of sensation[4,9]. If the autonomic nervous system is invaded, then abnormal body temperature and defecation and urination disorders may occur[10]. If syringomyelia affects the medulla oblongata, then paralysis and atrophy of the tongue, difficulty swallowing, dysarthria, and facial paralysis may occur[4]. If syringomyelia is not treated, the 10-year survival rate is known to be about 50%[4]. In particular, post-traumatic syringomyelia can range from transient neurological deficits due to minor trauma to complete paralysis of the upper and lower limbs[1,4,8].

To date, surgery has been the only treatment method for syringomyelia[4,11,12]. Surgical treatment for syringomyelia focuses on the cause of the cavity and reducing the pressure of the subarachnoid space, and the shunt is mainly used to draw fluid out from the cavity[13,14]. In the case of Chiari malformation, the subarachnoid space is enlarged with foramen magnum decompression and dura mater plastic surgery, and the cerebellar tonsils that obstruct the flow of cerebrospinal fluid are excised. However, these surgical treatments are suboptimal for the treatment of syringomyelia[15-17]. While this treatment prevents further nerve damage and can be expected to improve symptoms, there is a risk of complications such as bleeding, inflammation, and nerve damage. After surgery, symptoms may continue to worsen or the cavity may become enlarged[17]. Therefore, surgery is usually not performed unless symptoms worsen after the observation period of the patient’s progress.

In this study, we transplanted uncultured umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the purpose of alleviating pain in a patient with syringomyelia. At the beginning of treatment, it was expected that this treatment would be effective in relieving pain, but it was not expected that the syringomyelia would be cured. As intended, the patient’s disease-related pain gradually decreased. After the stem cell treatment, the patient also experienced an unexpected positive change which was observed during subsequent regular check-ups for follow-up after surgery for the Chiari malformation. First detected as a slight decrease in the patient’s cavity size, the shrinkage continued until the cavity had almost completely disappeared at 2 years after the stem cell treatment. Although we could not elucidate the underlying mechanism of this beneficial outcome, we expect that the transplantation of uncultured UC-MSCs may have produced a direct or indirect effect on both her syringomyelia and related Chiari malformation.

CASE PRESENTATION
Chief complaints

On May 25, 2016, a 59-year-old woman, suffering from syringomyelia, visited our clinic. The patient had extreme symptoms of pain and dysphonia. The patient reported suffering particularly from pain in the eye, hand, and knee, as well as myalgia and occipital headache.

History of present illness

The patient reported having started experiencing neck and hand pain after a fall in 2009, with those pain symptoms having persisted for more than 1 year. In July 2010, the patient was diagnosed with Chiari malformation with syringomyelia. The patient underwent foramen magnum decompression on November 22, 2010, to treat the Chiari malformation and syringomyelia. After surgery, however, the imaging analysis revealed no changes at the C6-T2 level of the spinal cord in the localized syringomyelia (Figure 1A and B). Subsequent magnetic resonance imaging investigations of the extended cervical spine were performed on August 29, 2011 and August 22, 2012, to check changes in the cavity’s size (Figure 1C-F). The data showed no significant changes at the C6-T2 level of the spinal cord in the localized cavity compared to imaging findings from 21 mo prior. The patient did not receive any additional treatment related to this disease other than the treatment received at our clinic after surgery.

Figure 1
Figure 1 Imaging analyses before and after stem cell treatment. A-F: Magnetic resonance imaging scans of the patient before stem cell treatment, from November 26, 2010 (A: Sagittal; B: Transverse), August 29, 2011 (C: Sagittal; D: Transverse) and August 21, 2012 (E: Sagittal; F: Transverse); G-J: Magnetic resonance imaging of the patient after stem cell treatment, from July 18, 2018 (G: Sagittal; H: Transverse) and August 31, 2020 (I: Sagittal; J: Transverse). Orange arrows indicate where the cavity is or was.
History of past illness

The patient had no specific disease, except for Chiari malformation with syringomyelia.

Personal and family history

The patient had no relevant personal and family disease histories.

Physical examination

At the time of the first visit, the patient participated in a brief question-and-answer session to confirm the symptoms. The patient’s pronunciation was not clear (but understandable) due to dysphonia. The patient also reported experiencing eye, hand, and knee pain, myalgia, and occipital headache at that time.

Laboratory examinations

Overall, there were no abnormalities on the routine blood and urine tests but total cholesterol (217 mg/dL; normal range: < 200 mg/dL) and low-density lipoprotein cholesterol (157 mg/dL; normal range: < 130 mg/dL) levels were borderline high.

Imaging examinations

Imaging examinations were not performed.

FINAL DIAGNOSIS

The patient was diagnosed with syringomyelia and was suffering from substantial pain and dysphonia.

TREATMENT
UC procurement

UCs were donated by the Obstetrics and Gynecology Department at Lynn Woman’s Hospital (Seoul, South Korea). The mothers who had donated the UCs had signed informed consent forms. All UCs were confirmed for safety through various tests of the mothers’ blood and urine.

Isolation and quality evaluation of UC-MSCs

UC-MSCs were obtained from the donated UCs. The isolation method is as follows[18-21]. The UCs were disinfected with 70% ethanol and washed with 1 × phosphate-buffered saline. Next, three vessels and the amniotic membrane were removed from the UCs. Then, the UC tissues were cut into 2-3 cm pieces and placed into a 50-mL conical tube containing collagenase and hyaluronidase mixture solution. The UC tissues were then cut into smaller pieces using surgical scissors and ground using a disposable tissue grinder. Following, the ground tissues were placed in a 37 °C incubator with 50 mL/L CO2 for 1 h. After filtration of the solution using a 100-μm filter, the UC-MSCs were harvested by centrifugation of the flow-through. The UC-MSCs were frozen using CryoStor® CS10 (Stemcell Technologies, Cambridge, MA, United States) and then stored at -80 °C for a day. The following day, the frozen cells were stored in liquid nitrogen.

The isolated UC-MSCs were analyzed by the expression level of MSC-specific proteins, such as CD73, CD90, and CD105. A CyFlow® Cube 6 (Sysmex, Lincolnshire, IL, United States) and FCS Express 5 software (De Novo Software, Glendale, CA, United States) were used. We only used cells that met the criteria of CD73 ≥ 70%, CD90 ≥ 90%, and CD105 ≥ 90% as a result of the analysis of the UC-MSCs. The UC-MSCs that were used also passed microbiological tests.

Preparation of injection solution

We prepared 6 × 107 cells per treatment to transplant into the patient, calculated for 1 × 106 cells per kg body weight. In order to lower the viscosity of the injection solution, we divided the cell content in half, for two solutions with each containing 3 × 107 uncultured UC-MSCs mixed with 10-mL of 0.9% normal saline solution for each.

Treatment

We chose the intravenous injection method instead of local injection into the painful area as the transplantation method because the patient was experiencing pain throughout the whole body. The 10-mL injection solutions (as above, containing 3 × 107 UC-MSCs) were diluted for use by adding to 100 mL of 0.9% normal saline solution. In one treatment, the patient was injected with this 110-mL solution two times. The first 110-mL injection was given over a period of 1-2 h. After a 1 h break, the patient received the second injection. The patient received a total of four treatments over 8 mo. In July 2018, the patient received an additional treatment (Table 1).

Table 1 Transplantation of uncultured umbilical cord-derived mesenchymal stem cells to the patient.
Treatment numberDateIn an injection
As a treatment
Cell amount
Volume in mL
Number of injections
Total cell amount
1May 25, 20163 × 107110 26 × 107
2July 26, 2016
3August 9, 2016
4January 13, 2017
5July 20, 2018
OUTCOME AND FOLLOW-UP

During the treatment period, the patient experienced repeated pain reductions and then recurrences. After receiving the first (May 25, 2016) and second (July 26, 2016) treatments, the effectiveness of the treatment did not last long. The effect of the third treatment (August 9, 2016), however, was maintained for about 5 mo, and on January 13, 2017, the patient received the fourth treatment. The patient maintained the pain-reducing effect for a long period.

After syringopleural foramen magnum decompression for the treatment of Chiari malformation, the patient attended regular check-ups for follow-up after the surgery at the hospital where the surgery had been performed. Interestingly, it was confirmed during the regular check-up in July 2018 that the cavity decreased in size (Figure 1G and H). Since the patient did not receive any treatment except for the uncultured UC-MSC transplantation, we considered the possibility that the stem cell treatment induced a reduction of the cavity size. Therefore, in July 2018, the patient received one more treatment. Afterward, the patient’s existing symptoms, such as eye, hand, and knee pain, myalgia, occipital headache, and dysphonia, improved significantly. As a result of imaging analysis performed in August 2020, the cavity was almost completely disappeared (Figure 1I and J). Since then, the patient has maintained a significant decrease in pain and dysphonia.

Report of side effects

The patient had temporary nausea and dizziness after the first treatment. However, these symptoms were not present in the second through fourth treatments. The patient did not report any particular side effects during the follow-up period.

DISCUSSION

MSCs have a paracrine effect that helps protect and regenerate neuronal cells and promotes the ability for differentiation into neuronal cells[22-24]. Recently, as MSC transplantation has shown therapeutic potential in patients with spinal cord injury, clinical cases using MSC transplantation are increasing[25,26]. Meanwhile, a Spanish research team reported the first case of MSC transplantation for a patient with post-traumatic syringomyelia in 2017, and the results of the follow-up study were announced in 2018[27,28]. So far, there have been only these two cases of syringomyelia treatment using cell therapy, and two additional studies using a syringomyelia model were reported in 2018 and 2020[29,30]. Although the mechanism of this benefit is not clear, as there are not many studies on MSCs and the treatment of syringomyelia, previous studies have shown that MSC transplantation has potential as an alternative treatment for syringomyelia.

The patient had undergone syringopleural foramen magnum decompression for the treatment of Chiari malformation with syringomyelia in 2010, but the syringomyelia remained. In the medical records issued by the hospital where the patient had been operated on, there was no significant change detected in the size of the cavity before 2014; however, there was a record of a slight decrease in the size of the cavity detected in March 2014. Unfortunately, since we could not secure magnetic resonance imaging (MRI), C-spine data was obtained in March 2014, but this precluded our ability to directly confirm the change in the size of the cavity. In addition, there was no record of syringomyelia in the medical record from March 2014 until May 25, 2016 (the start-day of UC-MSCs treatment). Therefore, based on the medical records and historic MRI C-spine results, we estimated that the patient’s cavity size before UC-MSC therapy was similar or slightly reduced compared to that before surgery. After four UC-MSC treatments had been administered over an 8-mo period, the patient showed cavity size that was significantly reduced according to the magnetic resonance imaging findings in 2018. Confirmed by magnetic resonance imaging, the cavity had almost disappeared in 2020.

Because the initial purpose of the UC-MSC-based treatment of this patient was pain relief, our data are insufficient to support the treatment of syringomyelia by MSCs. In particular, the absence of data for the imaging investigations carried out just before the stem cell treatment and the pressure change that occurred due to the reduction of the cavity’s size make it difficult to accurately interpret the study results. However, based on our results and findings from previous studies on the effect of MSC transplantation on syringomyelia, it is possible that MSC transplantation therapy plays a positive role in the treatment of syringomyelia patients[27-30]. We, therefore, expect that a future well-controlled and planned large-scale clinical study will provide support for this therapy as a new alternative for syringomyelia, which is particularly important since an appropriate treatment method is currently not available.

CONCLUSION

In this case study, a patient with syringomyelia was treated by intravenous transplantation of uncultured allogeneic UC-MSCs. Although this study is a case report for a single patient and there is room for interpretation of the data, considering the results of previously reported studies along with it, MSC transplantation may hold promise as a new treatment alternative for syringomyelia.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Cell and tissue engineering

Country/Territory of origin: South Korea

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): C, C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Bagheri-Mohammadi S, Iran; Ke X, China; Naserian S, France S-Editor: Fan JR L-Editor: A P-Editor: Fan JR

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