Use of Stem Cells in Orthopaedics



Fig. 16.1
Microfragmented adipose tissue





16.6 Results


Our study included a group of 20 patients with mean age of 61 years and OA of the knee grade 1, 2 and 3 according to the Kellgren–Lawrence classification.

In all the patients, the presence of osteoarthritis symptoms was confirmed by clinical examination, X-ray and MRI. Patients underwent a three-step procedure of lipoaspiration, adipose tissue processing and 6–10 mL reinjection into the knee through lateral suprapatellar approach. Results were assessed using KOOS questionnaire before the procedure (time zero) and then at 12 and 24 months’ follow-up. X-rays and MRI were also collected.

Significant increase in KOOS scores—Ten-point increase was considered minimal important change (MIC).

The improvement of the symptoms occurred few days after treatment and increased steadily throughout the whole period of the study in KOOS and VAS pain scale. On VAS (visual analogue scale), the evaluation of pain decreased from severe to mild.

The complications we observed after the procedure were temporary and not significant. There were subcutaneous haematomas and tissue fibrosis. We did not observe fever or infections.

It is worth noting that the greatest improvement was reported on the KOOS Sport scale. We believe this may be due to the fact that patients willing to undergo such a procedure were actively seeking for alternative treatment methods that would enable them to regain physical fitness, which had been impaired by pain. Hence the conclusion that Lipogems offers effective pain relief enables people with early osteoarthritis to continue with sports activities. Here we also present an interesting observation of regeneration of cartilage and meniscus tissue on one of treated patients.

The patient was a 60-year-old man with osteonecrosis of medial femoral condyle and osteoarthritis of medial compartment. Thirty years before he underwent subtotal medial meniscectomy, he was treated with high tibial osteotomy about 3 years before, but he was still complaining about the pain and stiffness of the knee. The patient was treated with single injection of microfragmented adipose tissue. After 3 months KOOS scores significantly improved as well as VAS pain scale. As shown in the 3T MRI (Fig. 16.1), we observed healing of the bone of medial, femoral and tibial condyles. In addition, we observed covering of the medial femoral condyle with newly formed cartilage-like and meniscus-like tissue in place of the removed medial meniscus. We also observed less fluid in the knee, which corresponded with clinically significant less swelling and functional improvement ( Fig. 16.2).

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Fig. 16.2
(Left) 3T MRI before microfragmented adipose injection; (right) 3T MRI 3 months after microfragmented adipose treatment injection


16.7 Introducing Platelet-Rich Stroma for the Treatment of Osteoarthritis


As an alternative to the method described above, the recently introduced procedure of fractionation is presented to fabricate a more pure stromal vascular fraction [ 26]. The microfragmentation technique mentioned before is about crushing a certain, undefined part of the adipocytes present in the lipoaspirate, and as such it does hold ASCs and adipocytes and does provide repair by the former cells as described above.

The newly described technique of mechanical fractionation of nearly all adipocytes from condensed lipoaspirate results in a 10 percent volume of stromal vascular fraction. This tissue-SVF is almost completely free of adipocytes and has the theoretical advantage of a much higher concentration of ASCs in a smaller volume. Seven to eight times more cells are present in only 10 percent volume of the initial condensed lipoaspirate. A 20 cc of regular decanted lipoaspirate will yield about 10 cc of condensed lipoaspirate after a first round of centrifugation (9.5 cm radius fixed-angle rotor for 4 min, Medilite™, Thermo Fisher Scientific, NY). Subsequently 10 cc of condensed lipoaspirate is swooshed 30x times forward and back over a fractionator (Tulip, 1.4 mm hole Luer-to-Luer-transfer, reusable or disposable). Second round of centrifugation, 3 min 3000 rpm, will deliver four fractions: 85% oil (ruptured adipocytes), 10% of tissue-stromal vascular fraction (t-SVF), 5% aqueous fraction with a small pellet (of mostly single cell SVF, c-SVF). These fractions can be easily separated rendering 10 percent volume of SVF, ready for injection.

Compared to the microfragmentation method described above, less lipoaspirate has to be harvested, reducing donor site morbidity. At the same time, more ASCs remain for injection in a smaller volume, allowing for delivering higher number of ASCs in their natural niche into smaller spaces with almost no adipocytes. Also the attributes needed are less expensive.

The senior author of the paper (Stevens, HP, co-author of this chapter) is a plastic surgeon, originally developed the technique to improve regeneration of damaged skin (for the treatment of damaged skin due to ageing, radiation or (surgical) trauma, scars). Based on earlier findings demonstrating that platelet-rich plasma (PRP) could reduce postinjection downtime by 30%, both retrospectively [ 27] and in a prospectively randomised clinical trial (personal communication, to be published), about 50 cases of PRP + SVF were performed. This combination is referred to as platelet-rich stroma (PRS).

Not only a clear improvement of skin quality was observed for scar tissue [ 26], but also aged facial skin assessed by VISIA UHD computer photography showed improvement, and alopecia androgenica that was treated with PRS showed a significant increase of hair density (Stevens HP et al., personal communication, to be published).

Case report of treating knee osteoarthritis with PRS with 6 months follow-up, WOMAC score is presented (Stevens HP, et al., submitted for publication). A 62-year-old male, former professional soccer player, was treated with a single intra-articular injection of PRS (platelet-rich stroma; PRP; and FAT-SVF, fractionated adipose tissue-stromal vascular fraction) in his left knee. The degree of osteoarthritic joint destruction was severe (Kellgren–Lawrence grade 3) and a total knee replacement was scheduled already. The FAT-SVF was prepared as described above. PRP was prepared by using the autologous conditioned plasma (ACP) double-syringe system. The emulsified mixture of 4 cc of PRP and 1 cc of FAT-SVF was injected through a lateral suprapatellar approach under local anaesthesia within 45 min ( Fig. 16.3). Prior injections with corticosteroids and hyaluronic acid did not result in any pain relief.

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Fig. 16.3
Injection of platelet-rich stroma (PRS); the mixture of platelet-rich plasma (PRP) with stromal vascular fraction (SVF) prepared by fractionation of adipose tissue (FAT) procedure)

Postinjection effects were measured using an adapted Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Directly within the first 2 weeks postinjection, pain and stiffness reduced significantly. Physical, social and emotional functioning improved dramatically. No adverse effects were noted. During increased physical activities from 4 to 8 weeks postinjection, a mild relapse of discomfort occurred. After taking some rest for a week, all parameters improved again up to 12 weeks postoperatively. Almost completely free of pain, not using any painkillers for weeks now, instead of having a total knee replacement, he was able to accept an offer as assistant football coach (in a professional international soccer club playing Champions League football). In the weeks thereafter, the increased activities and attempt to play ball a little bit resulted in increased pain. Painkillers were used again for 4 to 6 weeks. Reduction of physical stress and exercise allowed recovery of WOMAC scores as depicted to less than 50% of the original pre-injection levels of pain. Ultimately a knee replacement procedure might still be necessary at some date, but the socio-economical and financial benefit of the treatment and being able to postpone such an intervention are obvious.

This new procedure treating tissue damage by platelet-rich plasma enriched adipose stromal vascular fraction, and osteoarthritis (of the knee) in particular does seem promising and deserves further attention to our opinion.

Jul 31, 2017 | Posted by in ORTHOPEDIC | Comments Off on Use of Stem Cells in Orthopaedics

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