Stem cell injections for axial back pain: a systematic review of associated risks and complications with a case illustration of diffuse hyperplastic gliosis resulting in cauda equina syndrome

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OBJECTIVE

Axial low-back pain is a disease of epidemic proportions that exerts a heavy global toll on the active workforce and results in more than half a trillion dollars in annual costs. Stem cell injections are being increasingly advertised as a restorative solution for various degenerative diseases and are becoming more affordable and attainable by the public. There have been multiple reports in the media of these injections being easily available abroad outside of clinical trials, but scientific evidence supporting them remains scarce. The authors present a case of a serious complication after a stem cell injection for back pain and provide a systematic review of the literature of the efficacy of this treatment as well as the associated risks and complications.

METHODS

A systematic review of the literature was performed using the PubMed, Google Scholar, and Scopus online electronic databases to identify articles reporting stem cell injections for axial back pain in accordance with the PRISMA guidelines. The primary focus was on outcomes and complications. A case of glial hyperplasia of the roots of the cauda equina directly related to stem cell injections performed abroad is also reported.

RESULTS

The authors identified 14 publications (including a total of 147 patients) that met the search criteria. Three of the articles presented data for the same patient population with different durations of follow-up and were thus analyzed as a single study, reducing the total number of studies to 12. In these 12 studies, follow-up periods ranged from 6 months to 6 years, with 50% having a follow-up period of 1 year or less. Most studies reported favorable outcomes, although 36% used subjective measures. There was a tendency for pain relief to wane after 6 months to 2 years, with patients seeking a surgical solution. Only 1 study was a randomized controlled trial (RCT).

CONCLUSIONS

There are still insufficient data to support stem cell injections for back pain. Additional RCTs with long-term follow-up are necessary before statements can be made regarding the efficacy and safety.

ABBREVIATIONS MSC = mesenchymal stem cell; ODI = Oswestry Disability Index; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; UTSW = University of Texas Southwestern; VAS = visual analog scale.

Article Information

Correspondence Salah G. Aoun: The University of Texas Southwestern, Dallas, TX. salah.aoun@utsouthwestern.edu; salahaoun@hotmail.com.

INCLUDE WHEN CITING Published online September 6, 2019; DOI: 10.3171/2019.6.SPINE19594.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    PRISMA flow diagram of our systematic review.

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    Sagittal (A) and axial (B) T2-weighted MR images of the lumbar spine showing normal-appearing cauda equina nerve roots prior to stem cell injection.

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    Sagittal (A) and axial (B) T2-weighted MR images of the lumbar spine showing very hypertrophic nerve roots of the cauda equina with crowding of the spinal canal 18 months after stem cell injections.

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    Intraoperative image of the nerve roots of the cauda equina, with the dura opened and retracted, showing severe overgrowth of the nerves. Figure is available in color online only.

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    Sagittal (A) and axial (B) T2-weighted MR images of the lumbar spine obtained 3 months after surgery showing continued hypertrophy of the cauda equina roots.

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    Photomicrographs of H & E–stained sections showing well-differentiated piloid astrocytes that, in places, surround clusters of axons (A) and ependymal cells (B) with intracytoplasmic lumens (blue arrows). Original magnification ×100 (A) and ×200 (Β). Figure is available in color online only.

References

  • 1

    Amariglio NHirshberg AScheithauer BWCohen YLoewenthal RTrakhtenbrot L: Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6:e10000292009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    American Diabetes Association: Economic costs of diabetes in the U.S. in 2017. Diabetes Care 41:9179282018

  • 3

    Andersson GB: Epidemiological features of chronic low-back pain. Lancet 354:5815851999

  • 4

    Becker AJMcCulloch EATill JE: Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:4524541963

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Centeno CMarkle JDodson EStemper IWilliams CJHyzy M: Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy. J Transl Med 15:1972017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Comella KSilbert RParlo M: Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med 15:122017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    de Schepper EIDamen Jvan Meurs JBGinai AZPopham MHofman A: The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features. Spine (Phila Pa 1976) 35:5315362010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Elabd CCenteno CJSchultz JRLutz GIchim TSilva FJ: Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study. J Transl Med 14:2532016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Harrell CRMarkovic BSFellabaum CArsenijevic AVolarevic V: Mesenchymal stem cell-based therapy of osteoarthritis: current knowledge and future perspectives. Biomed Pharmacother 109:231823262019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Haufe SMMork AR: Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 15:1361372006

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Hurst RWBosch EPMorris JMDyck PJReeves RK: Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection. Muscle Nerve 48:8318352013 (Erratum in Muscle Nerve 49:298–303 2014)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Kirkland EBHeincelman MBishu KGSchumann SOSchreiner AAxon RN: Trends in healthcare expenditures among US adults with hypertension: national estimates, 2003–2014. J Am Heart Assoc 7:e0087312018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Kumar HHa DHLee EJPark JHShim JHAhn TK: Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther 8:2622017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Lee JWShin HIPark SYLee GYKang HS: Therapeutic trial of fluoroscopic interlaminar epidural steroid injection for axial low back pain: effectiveness and outcome predictors. AJNR Am J Neuroradiol 31:181718232010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Mead BBerry MLogan AScott RALeadbeater WScheven BA: Stem cell treatment of degenerative eye disease. Stem Cell Res (Amst) 14:2432572015

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Meisel HJSiodla VGaney TMinkus YHutton WCAlasevic OJ: Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 24:5212007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Mochida JSakai DNakamura YWatanabe TYamamoto YKato S: Intervertebral–disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety. Eur Cell Mater 29:2022122015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Noriega DCArdura FHernández-Ramajo RMartín-Ferrero MASánchez-Lite IToribio B: Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101:1945–19512017

    • Search Google Scholar
    • Export Citation
  • 19

    Oehme DGoldschlager TGhosh PRosenfeld JVJenkin G: Cell-based therapies used to treat lumbar degenerative disc disease: a systematic review of animal studies and human clinical trials. Stem Cells Int 2015:9460312015

    • Search Google Scholar
    • Export Citation
  • 20

    Orozco LSoler RMorera CAlberca MSánchez AGarcía-Sancho J: Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92:8228282011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Pang XYang HPeng B: Human umbilical cord mesenchymal stem cell transplantation for the treatment of chronic discogenic low back pain. Pain Physician 17:E525E5302014

    • Search Google Scholar
    • Export Citation
  • 22

    Pettine KSuzuki RSand TMurphy M: Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop 40:1351402016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Pettine KAMurphy MBSuzuki RKSand TT: Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells 33:1461562015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Pettine KASuzuki RKSand TTMurphy MB: Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop 41:209721032017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Rice CMScolding NJ: Adult stem cells—reprogramming neurological repair? Lancet 364:1931992004

  • 26

    Rivera CE: Lumbar epidural steroid injections. Phys Med Rehabil Clin N Am 29:73922018

  • 27

    Vadalà GSowa GHubert MGilbertson LGDenaro VKang JD: Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 6:3483552012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Yim RLLee JTBow CHMeij BLeung VCheung KM: A systematic review of the safety and efficacy of mesenchymal stem cells for disc degeneration: insights and future directions for regenerative therapeutics. Stem Cells Dev 23:255325672014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Yoshikawa TUeda YMiyazaki KKoizumi MTakakura Y: Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976) 35:E475E4802010

    • Crossref
    • Search Google Scholar
    • Export Citation

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