Stem Cell Therapy: articular cartilage and intervertebral disc regeneration - PowerPoint Presentation

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Stem Cell Therapy: articular cartilage and intervertebral disc regeneration

Benjamin Bonte, MD

Interventional pain fellow

Hudson Medical group

7/6/2018

Outline

Stem cells

Cartilage degeneration in osteoarthritis

Stem cells in cartilage regeneration

Back pain and intervertebral disc degeneration

Biology behind disc degeneration

Therapies for IVD degeneration

Literature review

conclusions

Stem cells

Excellent clinical success with hematopoietic stem cell transplantation for leukemia/lymphoma.

Outcomes for other use of stem cells remains poorly established/clinically validated.

Types:

Pluripotent – trilineage (embryonic stem cells, induced pluripotent stem cells)

Multipotent* - more than one lineage (bone marrow, adipose, umbilical cord)

Unipotent – single lineage

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering, Volume: 222, Issue: 1, Pages: 23-32, First published: 01 September 2009, DOI: (10.1002/jcp.21915)

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering, Volume: 222, Issue: 1, Pages: 23-32, First published: 01 September 2009, DOI: (10.1002/jcp.21915)

Current cartilage degeneration managemnt

Degeneration in chondrocytes with age results in impaired production of extracellular matrix proteins.

Tissue is hypocellular and poorly vascular.

DMOADs/NSAIDs, weight reduction, exercise.

Subchondral drilling/abrasion arthroplasty –long term efficacy is not known. Joint arthroplasty.

BM derived MSC for cardilage disorders.

Paracrine effects (growth factors, cytokines, bioactive lipids)

Antiinflammatory

,

angiopoietic

, and apoptotic effects.

Cellular differentiation

Intervertebral disc degeneration (IVD D)

PT, ESI, minimally invasive surgeries, disc implants, fusion

NP contains T2 collagen and

proteolgycans

which are hydrophilic.

Increased TNF alpha and IL1 expression leads to abnormal nerve ingrowth, matric degenerating enzymes

Switch from T2 to T1 collagen which deads to dehydration of matrix and loss of swelling pressure responsible for maintainngi mechanical integrity.Novel therapies include PRP which as growth factors that induce cell proliferation and matrix production.Nucluess pulposis is anabolic, with NP cells receiving energy through glycolysis and diffusion from vertebral bodies. Although preliminary results show positive effects, basic research suggest cells are unable to survive and adapt in the IVD.

BM harvest technique

Stem cell yield

1 in 10k to 1 in 50k of total nucleated cells

Viability and number are reduced by age and disease.

Different volumes should be considered.

More in an older person

“At least 60cc for a knee, 60 for

elbonw/ankle/shoulderSmall joint/intervertebral disc – 40-60ccVery small joint (finger, foot) – 30cc per side”

Optimizing yield

Drawing from multiple sites optimizes MSC yield, lower volume at each site.

Evidence for cartilage disorders

Goldring – case study.

24 weeks after injection, significant increases in cartilage and meniscus volume on MRI.

Increase ROM and decreased pain.

Sampson – 125 patients receiving hip, knee, shoulder, ankle, or cervical facet joint injection.

71% decrease in pain at 148 days.

Knee injections had best outcomesSatisfaction by 92% of patieints. 95% would recommend to a friend.

Evidence for Safety

Malanga

2372 patients who underwent stem cell injections with follow up of 2.2 years, 325 adverse events. 7 cases of neoplasm, lower rate than in the general population. Lowest rate of adverse events in BMC alone, compared with MVC + adipose and

culterd

cells.

Wakitani

41 patients who received 45 BM MSC injections with variable followup 5-137 monthsNo e/o infection or tumor growth.

Evidence in use for tendinopathy

Pascual Garrido et al

8 patients with refractory patellar tendinopathy

7 completely satisfied with injection at 5Y

followup

.

Statistically significant improvement in: Knee injury and osteoarthritis outcome scores, ADL, symptom, and sport subscores.Ellera Gomes et alStem cells used to augment conventional therapy in 14 patientsMRI analysis after 12m followup revaled tendon integrity.Hernigou and colleagues90 patients 10 years after routine arthroscopy +/- BMC injection.BMC treated group – 87% with intact RTCControl – 44% intact RTC.

Evidence for MSC in discogenic pain

The intervertebral disc is the largest avascular structure in the human body.

Nucluus

pulposus cells rely on glycolysis to produce energy.

Pettine and colleagues

26 patients, 13 single

leve, 13 two levelBeneficial effects with no disc worsening on MRI. 21 of 24 avoided surgery for 2 years with improvements in functional outcomes in pain.

Summary

Bone marrow derived mesenchymal stem cells is an exciting developing aspect of the field

Recent research suggest this can be used in the treatment of cartilage disorders/osteoarthritis, tendinopathy, and intervertebral disc disease.

Further research will help define the most appropriate and effective applications for these treatments.

Thank you!