Degenerative disc disease

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Degenerative disc disease
Other namesDegenerative disc disorder, intervertebral disc degeneration
Cervical Spine MRI showing degenerative changes closeup.jpg
Degenerated disc between C5 and C6 (vertebra at the top of the picture is C2), with osteophytes anteriorly (to the left) on the lower portion of the C5 and upper portion of the C6 vertebral body.
Specialty Orthopedics
Risk factors Connective tissue disease

Degenerative disc disease (DDD) is a medical condition typically brought on by the aging process in which there are anatomic changes and possibly a loss of function of one or more intervertebral discs of the spine. [1] DDD can take place with or without symptoms, but is typically identified once symptoms arise. The root cause is thought to be loss of soluble proteins within the fluid contained in the disc with resultant reduction of the oncotic pressure, which in turn causes loss of fluid volume. Normal downward forces cause the affected disc to lose height, and the distance between vertebrae is reduced. The anulus fibrosus, the tough outer layers of a disc, also weakens. This loss of height causes laxity of the longitudinal ligaments, which may allow anterior, posterior, or lateral shifting of the vertebral bodies, causing facet joint malalignment and arthritis; scoliosis; cervical hyperlordosis; thoracic hyperkyphosis; lumbar hyperlordosis; narrowing of the space available for the spinal tract within the vertebra (spinal stenosis); or narrowing of the space through which a spinal nerve exits (vertebral foramen stenosis) with resultant inflammation and impingement of a spinal nerve, causing a radiculopathy.

Contents

DDD can cause mild to severe pain, either acute or chronic, near the involved disc, as well as neuropathic pain if an adjacent spinal nerve root is involved. Diagnosis is suspected when typical symptoms and physical findings are present; and confirmed by x-rays of the vertebral column. Occasionally the radiologic diagnosis of disc degeneration is made incidentally when a cervical x-ray, chest x-ray, or abdominal x-ray is taken for other reasons, and the abnormalities of the vertebral column are recognized. The diagnosis of DDD is not a radiologic diagnosis, since the interpreting radiologist is not aware whether there are symptoms present or not. Typical radiographic findings include disc space narrowing, displacement of vertebral bodies, fusion of adjacent vertebral bodies, and development of bone in adjacent soft tissue (osteophyte formation). An MRI is typically reserved for those with symptoms, signs, and x-ray findings suggesting the need for surgical intervention.

Treatment may include physical therapy for pain relief, ROM, and appropriate muscle/strength training with emphasis on correcting abnormal posture, assisting the paravertebral (paraspinous) muscles in stabilizing the spine, and core muscle strengthening; stretching exercises; massage therapy; oral analgesia with non-steroidal anti-inflammatory agents (NSAIDS); and topical analgesia with lidocaine, ice and heat. Immediate surgery may be indicated if the symptoms are severe or sudden in onset, or there is a sudden worsening of symptoms. Elective surgery may be indicated after six months of conservative therapy with unsatisfactory relief of symptoms.

Signs and symptoms

Degenerative disc disease can result in lower back or upper neck pain. The amount of degeneration does not correlate well with the amount of pain patients experience. Many people experience no pain while others, with the same amount of damage have severe, chronic pain. [2] Whether a patient experiences pain or not largely depends on the location of the affected disc and the amount of pressure that is being put on the spinal column and surrounding nerve roots.

Degenerative disc disease is one of the most common sources of back pain and affects approximately 30 million people every year. [3] With symptomatic degenerative disc disease, the pain can vary depending on the location of the affected disc. A degenerated disc in the lower back can result in lower back pain, sometimes radiating to the hips, and pain in the buttocks, thighs, or legs. If pressure is being placed on the nerves by exposed nucleus pulposus, sporadic tingling or weakness through the knees and legs can occur.

A degenerated disc in the upper neck will often result in pain to the neck, arm, shoulders and hands; tingling in the fingers may also result if nerve impingement is occurring. Pain is most commonly felt or worsened by movements such as sitting, bending, lifting, and twisting.

After an injury, some discs become painful because of inflammation and the pain comes and goes. Some people have nerve endings that penetrate more deeply into the anulus fibrosus (outer layer of the disc) than others, making discs more likely to generate pain. The healing of trauma to the outer anulus fibrosus may also result in the innervation of the scar tissue and pain impulses from the disc, as these nerves become inflamed by nucleus pulposus material. Degenerative disc disease can lead to a chronic debilitating condition and can reduce a person's quality of life. When pain from degenerative disc disease is severe, traditional nonoperative treatment may be ineffective.

Cause

There is a disc between each of the vertebrae in the spine. A healthy, well-hydrated disc will contain a great deal of water in its center, known as the nucleus pulposus, which provides cushioning and flexibility for the spine. Much of the mechanical stress that is caused by everyday movements is transferred to the discs within the spine and the water content within them allows them to effectively absorb the shock. At birth, a typical human nucleus pulposus will contain about 80% water. [4] However natural daily stresses and minor injuries can cause these discs to gradually lose water as the annulus fibrosus, or the tough outer fibrous material of a disc, weakens. [5] Because degenerative disc disease is largely due to natural daily stresses, the American Academy of Orthopaedic Manual Physical Therapists have suggested it is not truly a "disease" process. [6]

This water loss makes the discs more flexible and results in the gradual collapse and narrowing of the gap in the spinal column. As the space between vertebrae gets smaller, extra pressure can be placed on the discs causing tiny cracks or tears to appear in the annulus. If enough pressure is exerted, it is possible for the nucleus pulposus material to seep out through the tears in the annulus and can cause what is known as a herniated disc.

As the two vertebrae above and below the affected disc begin to collapse upon each other, the facet joints at the back of the spine are forced to shift which can affect their function. [7]

Additionally, the body can react to the closing gap between vertebrae by creating bone spurs around the disc space in an attempt to stop excess motion. [8] This can cause issues if the bone spurs start to grow into the spinal canal and put pressure on the spinal cord and surrounding nerve roots as it can cause pain and affect nerve function. This condition is called spinal stenosis.

For women, there is evidence that menopause and related estrogen-loss are associated with lumbar disc degeneration, usually occurring during the first 15 years of the climacteric. The potential role of sex hormones in the etiology of degenerative skeletal disorders is being discussed for both genders. [9]

Mutations in several genes have been implicated in intervertebral disc degeneration. Probable candidate genes include type I collagen (sp1 site), type IX collagen, vitamin D receptor, aggrecan, asporin, MMP3, interleukin-1, and interleukin-6 polymorphisms. [10] Mutation in genes – such as MMP2 and THBS2 – that encode for proteins and enzymes involved in the regulation of the extracellular matrix has been shown to contribute to lumbar disc herniation. [11] [12]

Mechanisms

Micrograph of a fragment of a resected degenerative vertebral disc, showing degenerative fibrocartilage and clusters of chondrocytes. HPS stain. Degenerative disc disease - intermed mag.jpg
Micrograph of a fragment of a resected degenerative vertebral disc, showing degenerative fibrocartilage and clusters of chondrocytes. HPS stain.

Degenerative discs typically show degenerative fibrocartilage and clusters of chondrocytes, suggestive of repair. Inflammation may or may not be present. Histologic examination of disc fragments resected for presumed DDD is routine to exclude malignancy.

Fibrocartilage replaces the gelatinous mucoid material of the nucleus pulposus as the disc changes with age. There may be splits in the anulus fibrosus, permitting herniation of elements of nucleus pulposus. There may also be shrinkage of the nucleus pulposus that produces prolapse or folding of the anulus fibrosus with secondary osteophyte formation at the margins of the adjacent vertebral body. The pathologic findings in DDD include protrusion, spondylolysis, and subluxation of vertebrae (spondylolisthesis) and spinal stenosis. It has been hypothesized that Cutibacterium acnes may play a role. [13]

Diagnosis

Diagnosis of degenerative disc disease will usually consist of an analysis of a patient's individual medical history and an MRI to confirm the diagnosis and rule out other causes. [14] [15]

Treatment

Often, the symptoms of degenerative disc disease can be treated without surgery. One or a combination of treatments such as physical therapy, anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs, traction, or epidural steroid injection can provide adequate relief of troubling symptoms.

Surgery may be recommended if the conservative treatment options do not provide relief within two to three months for cervical or 6 months for lumbar symptoms. If leg or back pain limits normal activity, if there is weakness or numbness in the legs, if it is difficult to walk or stand, or if medication or physical therapy are ineffective, surgery may be necessary, most often spinal fusion. There are many surgical options for the treatment of degenerative disc disease, including anterior [16] and posterior approaches. The most common surgical treatments include: [17]

Traditional approaches in treating patients with DDD-resultant herniated discs oftentimes include discectomy—which, in essence, is a spine-related surgical procedure involving the removal of damaged intervertebral discs (either whole removal, or partially-based). The former of these two discectomy techniques involved in open discectomy is known as Subtotal Discectomy (SD; or, aggressive discectomy) and the latter, Limited Discectomy (LD; or, conservative discectomy). However, with either technique, the probability of post-operative reherniation exists and at a considerably high maximum of 21%, prompting patients to potentially undergo recurrent disk surgery. [18]

New treatments are emerging that are still in the beginning clinical trial phases. Glucosamine injections may offer pain relief for some without precluding the use of more aggressive treatment options.[ citation needed ] Adult stem cell or cell transplantation therapies for disc regeneration are in their infancy of development, but initial clinical trials have shown cell transplantation to be safe and initial observations suggest some beneficial effects for associated pain and disability. [19] [20] An optimal cell type, transplantation method, cell density, carrier, or patient indication remains to be determined. Investigation into mesenchymal stem cell therapy knife-less fusion of vertebrae in the United States began in 2006 [21] and a DiscGenics nucleus pulposus progenitor cell transplantation clinical trial has started as of 2018 in the United States [22] and Japan. [23]

Researchers and surgeons have conducted clinical and basic science studies to uncover the regenerative capacity possessed by the large animal species involved (humans and quadrupeds) for potential therapies to treat the disease. [24] Some therapies, carried out by research laboratories in New York, include introduction of biologically engineered, injectable riboflavin cross-linked high density collagen (HDC-laden) gels into disease spinal segments to induce regeneration, ultimately restoring functionality and structure to the two main inner and outer components of vertebral discs—anulus fibrosus and the nucleus pulposus. [25]

Other animals

Degenerative disc disease can occur in other mammals besides humans. It is a common problem in several dog breeds, such as the Dachshund, and attempts to remove this disease from dog populations have led to several hybrid breeds, such as the Chiweenie. [26]

See also

Related Research Articles

<span class="mw-page-title-main">Back pain</span> Area of body discomfort

Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia based on the segment affected. The lumbar area is the most common area affected. An episode of back pain may be acute, subacute or chronic depending on the duration. The pain may be characterized as a dull ache, shooting or piercing pain or a burning sensation. Discomfort can radiate to the arms and hands as well as the legs or feet, and may include numbness or weakness in the legs and arms.

<span class="mw-page-title-main">Intervertebral disc</span> Cartilage of spine

An intervertebral disc lies between adjacent vertebrae in the vertebral column. Each disc forms a fibrocartilaginous joint, to allow slight movement of the vertebrae, to act as a ligament to hold the vertebrae together, and to function as a shock absorber for the spine.

<span class="mw-page-title-main">Sciatica</span> Lower back pain that extends down leg

Sciatica is pain going down the leg from the lower back. This pain may go down the back, outside, or front of the leg. Onset is often sudden following activities like heavy lifting, though gradual onset may also occur. The pain is often described as shooting. Typically, symptoms are only on one side of the body. Certain causes, however, may result in pain on both sides. Lower back pain is sometimes present. Weakness or numbness may occur in various parts of the affected leg and foot.

<span class="mw-page-title-main">Discectomy</span> Surgical removal of an intervertebral disc

A discectomy is the surgical removal of abnormal disc material that presses on a nerve root or the spinal cord. The procedure involves removing a portion of an intervertebral disc, which causes pain, weakness or numbness by stressing the spinal cord or radiating nerves. The traditional open discectomy, or Love's technique, was published by Ross and Love in 1971. Advances have produced visualization improvements to traditional discectomy procedures, or endoscopic discectomy. In conjunction with the traditional discectomy or microdiscectomy, a laminotomy is often involved to permit access to the intervertebral disc. Laminotomy means a significant amount of typically normal bone is removed from the vertebra, allowing the surgeon to better see and access the area of disc herniation.

<span class="mw-page-title-main">Lumbar spinal stenosis</span> Narrowing of the lower spinal canal

Lumbar spinal stenosis (LSS) is a medical condition in which the spinal canal narrows and compresses the nerves and blood vessels at the level of the lumbar vertebrae. Spinal stenosis may also affect the cervical or thoracic region, in which case it is known as cervical spinal stenosis or thoracic spinal stenosis. Lumbar spinal stenosis can cause pain in the low back or buttocks, abnormal sensations, and the absence of sensation (numbness) in the legs, thighs, feet, or buttocks, or loss of bladder and bowel control.

<span class="mw-page-title-main">Spondylosis</span> Degeneration of the vertebral column

Spondylosis is the degeneration of the vertebral column from any cause. In the more narrow sense it refers to spinal osteoarthritis, the age-related degeneration of the spinal column, which is the most common cause of spondylosis. The degenerative process in osteoarthritis chiefly affects the vertebral bodies, the neural foramina and the facet joints. If severe, it may cause pressure on the spinal cord or nerve roots with subsequent sensory or motor disturbances, such as pain, paresthesia, imbalance, and muscle weakness in the limbs.

<span class="mw-page-title-main">Spinal fusion</span> Immobilization or ankylosis of two or more vertebrae by fusion of the vertebral bodies

Spinal fusion, also called spondylodesis or spondylosyndesis, is a surgery performed by orthopaedic surgeons or neurosurgeons that joins two or more vertebrae. This procedure can be performed at any level in the spine and prevents any movement between the fused vertebrae. There are many types of spinal fusion and each technique involves using bone grafting—either from the patient (autograft), donor (allograft), or artificial bone substitutes—to help the bones heal together. Additional hardware is often used to hold the bones in place while the graft fuses the two vertebrae together. The placement of hardware can be guided by fluoroscopy, navigation systems, or robotics.

<span class="mw-page-title-main">Spinal disc herniation</span> Injury to the connective tissue between spinal vertebrae

A spinal disc herniation is an injury to the intervertebral disc between two spinal vertebrae, usually caused by excessive strain or trauma to the spine. It may result in back pain, pain or sensation in different parts of the body, and physical disability. The most conclusive diagnostic tool for disc herniation is MRI, and treatment may range from painkillers to surgery. Protection from disc herniation is best provided by core strength and an awareness of body mechanics including good posture.

<span class="mw-page-title-main">Radiculopathy</span> Medical condition

Radiculopathy, also commonly referred to as pinched nerve, refers to a set of conditions in which one or more nerves are affected and do not work properly. Radiculopathy can result in pain, weakness, altered sensation (paresthesia) or difficulty controlling specific muscles. Pinched nerves arise when surrounding bone or tissue, such as cartilage, muscles or tendons, put pressure on the nerve and disrupt its function.

<span class="mw-page-title-main">Anterior cervical discectomy and fusion</span> Surgical procedure

Anterior cervical discectomy and fusion (ACDF) is a surgical procedure to treat nerve root or spinal cord compression by decompressing the spinal cord and nerve roots of the cervical spine with a discectomy, followed by inter-vertebral fusion to stabilize the corresponding vertebrae. This procedure is used when other non-surgical treatments have failed.

<span class="mw-page-title-main">Cervical spinal stenosis</span> Narrowing of the upper spinal canal

Cervical spinal stenosis is a bone disease involving the narrowing of the spinal canal at the level of the neck. It is frequently due to chronic degeneration, but may also be congenital. Treatment is frequently surgical.

<span class="mw-page-title-main">Neurogenic claudication</span> Discomfort in the legs during walking due to nerve impingement

Neurogenic claudication (NC), also known as pseudoclaudication, is the most common symptom of lumbar spinal stenosis (LSS) and describes intermittent leg pain from impingement of the nerves emanating from the spinal cord. Neurogenic means that the problem originates within the nervous system. Claudication, from Latin claudicare 'to limp', refers to painful cramping or weakness in the legs. NC should therefore be distinguished from vascular claudication, which stems from a circulatory problem rather than a neural one.

<span class="mw-page-title-main">Spinal decompression</span> Relief of pressure on the spinal cord or compressed nerve roots

Spinal decompression is the relief of pressure on the spinal cord or on one or more compressed nerve roots passing through or exiting the spinal column. Decompression of the spinal neural elements is a key component in treating spinal radiculopathy, myelopathy and claudication.

<span class="mw-page-title-main">Lumbar provocative discography</span>

Lumbar provocative discography is an invasive diagnostic procedure for evaluation for intervertebral disc pathology. It is usually reserved for persons with persistent, severe low back pain (LBP) who have abnormal spaces between vertebrae on magnetic resonance imaging (MRI), where other diagnostic tests have failed to reveal clear confirmation of a suspected disc as the source of pain, and surgical intervention is being considered.

<span class="mw-page-title-main">Disc protrusion</span> Medical condition in which spinal cartilage bulges outward under pressure but remains intact

A disc protrusion is a medical condition that can occur in some vertebrates, including humans, in which the outermost layers of the anulus fibrosus of the intervertebral discs of the spine are intact but bulge when one or more of the discs are under pressure.

<span class="mw-page-title-main">Spinal stenosis</span> Disease of the bony spine that results in narrowing of the spinal canal

Spinal stenosis is an abnormal narrowing of the spinal canal or neural foramen that results in pressure on the spinal cord or nerve roots. Symptoms may include pain, numbness, or weakness in the arms or legs. Symptoms are typically gradual in onset and improve with leaning forward. Severe symptoms may include loss of bladder control, loss of bowel control, or sexual dysfunction.

The TESSYS method is a minimally-invasive, endoscopic spinal procedure for the treatment of a herniated disc. It was a further development of the YESS method by the Dutch Dr Thomas Hoogland in the Alpha Klinik in Munich in 1989 and was first called THESSYS. The procedure involves performing a small foramenotomy and removal of soft tissue compressing the nerve root.

<span class="mw-page-title-main">Vertebral column</span> Bony structure found in vertebrates

The vertebral column, also known as the spinal column, spine or backbone, is the core part of the axial skeleton in vertebrate animals. The vertebral column is the defining and eponymous characteristic of the vertebrate endoskeleton, where the notochord found in all chordates has been replaced by a segmented series of mineralized irregular bones called vertebrae, separated by fibrocartilaginous intervertebral discs. The dorsal portion of the vertebral column houses the spinal canal, an elongated cavity formed by alignment of the vertebral neural arches that encloses and protects the spinal cord, with spinal nerves exiting via the intervertebral foramina to innervate each body segments.

Astronauts have expressed an increased incidence of back pain during spaceflight and herniated intervertebral discs (IVD) have been diagnosed upon return of Skylab and Shuttle spaceflight participants.

<span class="mw-page-title-main">Vertebra</span> Bone in the vertebral column

Each vertebra is an irregular bone with a complex structure composed of bone and some hyaline cartilage, that make up the vertebral column or spine, of vertebrates. The proportions of the vertebrae differ according to their spinal segment and the particular species.

References

  1. ↑ Fardon, David F.; Williams, Alan L.; Dohring, Edward J.; Murtagh, F. Reed; Gabriel Rothman, Stephen L.; Sze, Gordon K. (November 2014). "Lumbar Disc Nomenclature: Version 2.0". Spine. 39 (24): E1448–E1465. doi: 10.1097/BRS.0b013e3182a8866d . PMID   23970106. S2CID   8931118.
  2. ↑ Izzo, R (May 2015). "Spinal Pain". Eur J Radiol. 84 (5): 746–756. doi:10.1016/j.ejrad.2015.01.018. PMID   25824642 . Retrieved June 20, 2022.
  3. ↑ "Degenerative Disc Disease Treatment|Degeneratice Disc Disease Treatments". www.instituteforchronicpain.org. Retrieved 2017-01-05.
  4. ↑ Kasbia, Virinder (8 September 2005). "Degenerative disc disease". Pembroke Observer. p. 7. ProQuest   354183403.
  5. ↑ "Degenerative Disc Disease". University of Maryland Medical Center. Retrieved 2017-01-04.
  6. ↑ Emerson AJ, Naze G, Mabry LM, Chaconas E, Silvernail J, Lonnemann E, Rhon D, Deyle GD. "AAOMPT Opposes Use of the Term "Degenerative Disc Disease"". American Academy of Orthopaedic Manual Physical Therapists Member's Resources Page. Retrieved 2019-12-31.
  7. ↑ Lee, Yu Chao; Zotti, Mario Giuseppe Tedesco; Osti, Orso Lorenzo (2016). "Operative Management of Lumbar Degenerative Disc Disease". Asian Spine Journal. 10 (4): 801–19. doi:10.4184/asj.2016.10.4.801. PMC   4995268 . PMID   27559465.
  8. ↑ "Bone spurs Causes – Mayo Clinic". Mayo Clinic. Retrieved 2017-01-04.
  9. ↑ Lou, C.; Chen, H-L.; Feng, X-Z.; Xiang, G-H.; Zhu, S-P.; Tian, N-F.; Jin, Y-L.; Fang, M-Q.; Wang, C.; Xu, H-Z. (December 2014). "Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs". Climacteric. 17 (6): 700–704. doi:10.3109/13697137.2014.933409. PMID   25017806. S2CID   20841659.
  10. ↑ Anjankar SD, Poornima S, Raju S, Jaleel M, Bhiladvala D, Hasan Q. Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism: A preliminary case control study of Indian population. Indian J Orthop 2015;49:589-94
  11. ↑ Kawaguchi, Y. (2018). "Genetic background of degenerative disc disease in the lumbar spine". Spine Surgery and Related Research. 2 (2): 98–112. doi:10.22603/ssrr.2017-0007. PMC   6698496 . PMID   31440655.
  12. ↑ Hirose, Yuichiro; et al. (May 2008). "A Functional Polymorphism in THBS2 that Affects Alternative Splicing and MMP Binding Is Associated with Lumbar-Disc Herniation". American Journal of Human Genetics. 82 (5): 1122–1129. doi:10.1016/j.ajhg.2008.03.013. PMC   2427305 . PMID   18455130.
  13. ↑ Capoor, Manu N.; Ruzicka, Filip; Schmitz, Jonathan E.; James, Garth A.; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S.; Alamin, Todd F.; Anand, Neel; Baird, John C.; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K.; Fisher, Steve; Garfin, Steven R.; Gogia, Jaspaul S.; Gokaslan, Ziya L.; Kuo, Calvin C.; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A. Nick; Stewart, Philip S.; Stonemetz, Jerry L.; Wang, Jeffrey C.; Witham, Timothy F.; Coscia, Michael F.; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej (3 April 2017). "Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy". PLOS ONE. 12 (4): e0174518. Bibcode:2017PLoSO..1274518C. doi: 10.1371/journal.pone.0174518 . PMC   5378350 . PMID   28369127.
  14. ↑ Farshad-Amacker, Nadja A.; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav (2015). "MR imaging of degenerative disc disease". European Journal of Radiology. 84 (9). Elsevier BV: 1768–1776. doi:10.1016/j.ejrad.2015.04.002. ISSN   0720-048X. PMID   26094867.
  15. ↑ "How Fast Does Degenerative Disc Disease Progress?". 7 September 2023.
  16. ↑ Sugawara, Taku (2015). "Anterior Cervical Spine Surgery for Degenerative Disease: A Review". Neurologia Medico-Chirurgica. 55 (7): 540–546. doi:10.2176/nmc.ra.2014-0403. PMC   4628186 . PMID   26119899.
  17. ↑ "Degenerative Disc Disease – When Surgery Is Needed" . Retrieved 2007-06-26.
  18. ↑ Shin, Byung-Joon (2014). "Risk factors for recurrent lumbar disc herniations". Asian Spine Journal. 8 (2): 211–215. doi:10.4184/asj.2014.8.2.211. PMC   3996348 . PMID   24761206.
  19. ↑ Schol, Jordy; Sakai, Daisuke (April 2019). "Cell therapy for intervertebral disc herniation and degenerative disc disease: clinical trials". International Orthopaedics. 43 (4): 1011–1025. doi: 10.1007/s00264-018-4223-1 . PMID   30498909. S2CID   53981159.
  20. ↑ Sakai, Daisuke; Schol, Jordy (April 2017). "Cell therapy for intervertebral disc repair: Clinical perspective". Journal of Orthopaedic Translation. 9: 8–18. doi: 10.1016/j.jot.2017.02.002 . PMC   5822958 . PMID   29662795.
  21. ↑ "Mesoblast files spinal fusion IND". Australian Life Scientist. 2006-11-27. Archived from the original on 2009-01-08. Retrieved 2009-02-16.
  22. ↑ "NCT03347708". ClinicalTrials.gov. 2 March 2020.
  23. ↑ "DiscGenics Receives Approval from Japanese Pharmaceuticals and Medical Devices Agency to Begin Clinical Evaluation of Non-Surgical Degenerative Disc Disease Treatment in Japan". PR News Wire.
  24. ↑ Moriguchi, Yu; Alimi, Marjan; Khair, Thamina; Manolarakis, George; Berlin, Connor; Bonassar, Lawrence J.; Härtl, Roger (2016). "Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data". Global Spine Journal. 6 (5): 497–518. doi:10.1055/s-0036-1571955. PMC   4947401 . PMID   27433434.
  25. ↑ Pennicooke, Brenton; Hussain, Ibrahim; Berlin, Connor; Sloan, Stephen R.; Borde, Brandon; Moriguchi, Yu; Lang, Gernot; Navarro-Ramirez, Rodrigo; Cheetham, Jonathan; Bonassar, Lawrence J.; Härtl, Roger (February 2018). "Annulus Fibrosus Repair Using High-Density Collagen Gel: An In Vivo Ovine Model". Spine. 43 (4): E208–E215. doi:10.1097/BRS.0000000000002334. PMC   6686199 . PMID   28719551.
  26. ↑ "Chiweenie - Dogs 101 | Animal Planet". www.animalplanet.com. Retrieved 2017-12-20.
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