Saturday, November 9, 2013

How Well Do Adult Stem Cells Work For Osteoarthritis of the Knee?


Current treatments for osteoarthritis of the knee (OAK) are inadequate. They provide symptom relief only and do not restore articular cartilage.

This is an excerpt from a presentation at the American College of Rheumatology meeting on an ultrasound-guided procedure using autologous mesenchymal stem cells, growth factors, and fat matrix (GMSCL).

The working hypothesis was: autologous stem cells from bone marrow can be stimulated to grow cartilage if provided with...

• A proper scaffold
• Autologous growth stimulating factors
• Limited weight-bearing

Our patient profile consisted of the following...

• 22 patients
• 36-64 years of age
• 16 men; 6 women
• BMI: 21-36.1
• Kellgren-Lawrence class:
o 6 grade 2
o 10 grade 3
o 6 grade 4

In preparation, patients were given the following instructions...

• No NSAIDS (oral and topical) for one month prior and one month post
• No fish oil for one month prior and one month post
• May continue prophylactic baby aspirin
• No intraarticular injections of any kind 1 month prior or during 1 year follow up.

Our procedure can be considered analogous to "Preparing a Garden"

• Sixty cc's marrow harvested posterior iliac crest (5 cc's stem cell concentrate~ 6 million stem cells)- "seeds"
• Sixty cc's peripheral blood for creation of platelet -rich plasma (5 cc's)- "fertilizer"
• Fifteen cc's fat from abdomen or flank- "soil"

Ultrasound guided fenestration was performed in all patients.

• Purpose: stimulate acute inflammatory response
• Joint capsule sites
- joint line
- adductor tubercle
- medial patellar facet

Regional treatment of fenestrated areas and joint was followed by direct ultrasound-guided instillation of...

• Stem cells
• Platelet-rich plasma
• Subcutaneous fat
• Calcium chloride/thrombin

Post-procedure, patients were given the following instructions...

• Non-weight-bearing for two weeks
• Limited weight-bearing with brace that unloads affected compartment for four to six weeks

A summary of our results is as follows...

Data Available

• 11 Patients at 6 months
• 10 Patients at 12 months

Treatment failures

• Four patients
• Defined as patients with no clinical improvement after three months

Two other "failures"

• One person died of an unrelated illness
• One person lived too far away to come back

Five patients haven't hit the six month mark

WOMAC

? 6 Months= -19.9

SD=17.92

SEM= 5.67

? 12 Months= -7.9

SD= 9.97

SEM= 3.15

Patient VAS Pain

? 6 Months=-33.7

SD= 16.71

SEM= 5.57

? 12 Months= -25.2

SD= 25.94

SEM= 8.20

Patient Global Assessment

? 6 Months= -33.0

SD= 24.13

SEM= 8.05

? 12 Months= -33.1

SD= 19.04

SEM= 6.35

Patient 50 Foot Walk Pain

? 6 Months= -26.3

SD= 15.54

SEM= 4.91

? 12 Months= -16.7

SD= 12.05

SEM= 4.01

Physician Global Assessment

? 6 Months= -51.2

SD= 21.60

SEM= 6.83

? 12 Months= -53.0

SD= 24.15

SEM= 8.54

Placebo effect? Probably not...

Example of Celebrex vs placebo in OA trials

Mean composite WOMAC score (pain, stiffness, physical function) = -5.7 (-7.5 to -3.9)

[Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial.Mayo Clin Proc 1999;74: 1095-1105; Zhao SZ, McMillen JI, Markenson JA, Dedhiya SD, Zhao WW, Osterhaus JT, et al.Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib. Pharmacotherapy 1999;19: 1269-1278].

Ultrasound measurement of patello-femoral cartilage thickness at 7 standardized points

• Knee flexed to 90 degrees
• Identical sites matched for accuracy
• Five measurements each point for reproducibility
• High and low dropped and the three middle averaged

Ultrasound measurement of patello-femoral cartilage thickness at 7 standardized points

• Mean improvement from baseline to 6 months (11 pts) - 0.4 mm
• Mean improvement from baseline to 12 months (10 pts) - 0.8 mm

Conclusion

While it is an uncontrolled study, GMSCL demonstrates some promise as a treatment for OAK. Further study is recommended

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