Orthopedist of San Fran aiming at Arthritis Treatment with Stem Cells
(from webpage of Stone Research Foundation)
May 5, 2014
About The Stone Research Foundation
The Stone Research Foundation leverages small amounts of capital into important clinical and translational research and education. In our clinical research, we conduct outcome studies to measure the effectiveness of the biologic surgical techniques developed and utilized at The Stone Clinic. We conduct translational research to prove the scientific merit of new biologic approaches. And, we disseminate of the results of this research through presentation, publication, and education in order that others may benefit.
Arthritis Ruins Lives
Arthritis is a silent, insidious, and painful joint disorder that ruins many lives. In the United States, it’s the most common cause of disability. Around 50 million adults in the US have some form of arthritis. That’s 1 in 4 adults. By 2030, an estimated 67 million American adults are projected to have physician-diagnosed arthritis.
The Case for Articular Cartilage Paste Grafting.
In 1991, we developed the “Articular Cartilage Paste Grafting” technique to provide a simple and cost-effective method to treat acute and chronic osteocartilaginous lesions in both healthy and arthritic knees. The rationale behind the invention of this technique was that if marrow cells were released from the bone marrow below a defect and came in contact with signaling factors in the extracellular matrix of cartilage, then those pluripotential cells and the chondrocytes in cartilage could form healthy repair tissue if combined with bone and impacted into a morselized lesion with a matrix of bone. The lesion had to be morselized, or super microfractured, to stimulate a significant healing response. We learned that the paste only had to fill the holes and not fill-up the lesion as hypertrophy was noted in the follow-up evaluations. Seventy biopsies of the first 125 paste graftings were reviewed by an independent histopathologist, who noted that biopsies from one-third of the lesions had grown cartilage indistinguishable from normal, one-third appeared to be a mix of fibrocartilage and hyaline cartilage and one-third appeared to be solely fibrous tissue.
H & E, PERPENDICULAR TO ARTICULAR SURFACE, 16X
SAFRANIN-O/FAST GREEN, PERPENDICULAR TO ARTICULAR SURFACE, 16X
Several studies have extended our findings on the paste grafting procedure and we are excited to share these with you. The most important is a rabbit study by Xing et al. comparing the paste graft technique to microfracture. The key points from this study are:
- “At 12 weeks, paste-grafted lesions were totally filled with smooth white cartilaginous tissue that was similar to surrounding tissue, while the microfractured lesions were filled with a yellow and white overlapping tissue that was thinner and more fragile than the surrounding cartilage.
- The DNA-normalized GAG content of the repair tissue showed a time-dependent increase with significant differences between groups at 8 and 12 weeks.
- Paste grafting appears to improve repair tissue by utilizing a greater quantity of pluripotential cells, cartilage matrix, and viable chondrocytes, creating a synergistic interaction between all three that results in greater production of collagen II and aggrecan.
- The paste grafted lesions showed a reduced width of the acellular zone compared to the microfracture group.”
The second study of importance is a comparative analysis by Kon et al. of patients with osteochondritis dissecans of the knee who were treated with various repair techniques. This study from Bologna, confirmed that “the results in OCD of ACI, MaioRegen and paste grafting all were effective in achieving good clinical and radiographic results.” But only paste grafting is without additional cost. Some key points from this study:
- 10 patients undergoing paste grafting at an average age of 24.4 years (3 female, 7 male)
- Average lesion size of 2.9 cc (second largest of the 5 groups in the study)
- Average follow-up of 3.8 years
- Pain and function score (IKDC) was significantly higher at final follow-up than preop
- The study highlights the key advantages of the procedure
- single surgical session
- minimal donor site morbidity
Thirdly, a rabbit study, performed by Jaroszewski et al. from Poland, studied the cartilage repair tissue formed after a 12-week in-life period. The investigators concluded that “the results indicated that application of the osteochondral paste in treatment of cartilage defects yields a stable, highly cellular tissue, resistant to time and trauma.” Some key points from this study:
- Study in rabbits (25 adult rabbits) with follow-up at 4, 8 and 12 weeks.
- Three groups were observed: (1) paste graft; (2) paste graft with a tissue covering; (3) untreated defects.
- The authors found that:
- paste graft filled the defects the best and with cartilage very similar to regular, healthy articular cartilage
- the repair tissue formed by the paste graft was well-integrated with the surrounding tissue in the knee; almost all subchondral bone was rebuilt
- early follow-up (4 weeks) showed a high tissue turnover rate, suggesting that the grafted paste dies off while the repair tissue is formed
- this turnover slows with time; showing increasing stability of the formed repair tissue.
- long-term follow-up (12 weeks) showed high cellularity (95% compared to surrounding tissue)
The Stone Research Foundation has published our 2 – 12 year outcome data of arthritic patients undergoing combined paste grafting and meniscus transplantation with excellent survival of the implant and preservation of the improved clinical results and is completing our 10 – 20 year follow-ups on our original paste grafting group.
We believe that paste grafting represents a cost-effective, one-step outpatient procedure that deserves consideration for acute and chronic cartilage lesions. And, we believe that arthritis can and should be successfully treated returning patients to active lifestyles rather than palliative treatment with drugs and activity modification. We hope you agree and we look forward to your input.
1. Jaroszewski J, Kruczynski J, Piontek T, Trzeciak T, Lubiatowski P. [The value of autologous osteochondral paste for in-vitro treatment of damage to articular cartilage. Part I. Macroscopic and microscopic assessment of the regenerated articular surface]. Chir Narzadow Ruchu Ortop Pol 2003;68-4:237-41.
2. Jaroszewski J, Kruczynski J, Piontek T, Trzeciak T, Kaszuba B, Lubiatowski P. [Value of autologous transplantation of osteo-chondral paste in reconstruction of experimental cartilage defects. Part II. Microscopic analysis of integration with surrounding cartilage, structural integrity and subchondral bone reconstruction in repair tissue]. Chir Narzadow Ruchu Ortop Pol 2003;68-5:335-40.
3. Jaroszewski J, Kruczynski J, Trzeciak T, Lubiatowski P, Kaszuba B. [Value of osteo-chondral paste autologous transplantation in experimental cartilage defects reconstruction. Part III–Microscopic analysis of reconstructed cartilage thickness and surface regularity]. Chir Narzadow Ruchu Ortop Pol 2004;69-1:35-9.
4. Jaroszewski J, Kruczynski J, Trzeciak T, Piontek T, Kaszuba B. [Value of osteo-chondral paste autologous transplantation in experimental cartilage defects reconstruction. Part IV–Microscopic analysis of cellularity and of traits of necrosis in the defect-filling tissue].Chir Narzadow Ruchu Ortop Pol 2004;69-2:115-9.
5. Kon E, Vannini F, Buda R, Filardo G, Cavallo M, Ruffilli A, Nanni M, Di Martino A, Marcacci M, Giannini S. How to treat osteochondritis dissecans of the knee: surgical techniques and new trends: AAOS exhibit selection. J Bone Joint Surg Am 2012;94-1:e1(-8).
6. Xing L, Jiang Y, Gui J, Lu Y, Gao F, Xu Y. Microfracture combined with osteochondral paste implantation was more effective than microfracture alone for full-thickness cartilage repair. Knee Surg Sports Traumatol Arthrosc 2013;21-8:1770-6.