Non-surgical repair of Hip and Knee OA: Adipose Derived Stem Cell Therapy Can Improve OA with Minimal Downtime

What is Osteoarthritis (OA) of the hips and knees, and how can it be helped with Stem Cell Therapy?

At Oregon Regenerative Medicine, we use an integrated system of natural therapies combined with Adipose Derived Stem Cell Therapy to compliment conventional treatment of OA.

Osteoarthritis is the most common joint disease in humans. According to Harrison’s Manual of Medicine, over 1,000,000 people have impaired walking capabilities due to osteoarthritis of the hips or knees. Osteoarthritis is characterized by destruction of the cartilage and cushioning surfaces of joints.  This destruction of the cartilage can be brought on by overuse, injury, and generalized inflammation. Research also shows that a deficiency in specific nutrients, including vitamin D, can accelerate and lead to cartilage distress. The most common joints we treat are hip, knee, ankle, shoulder, finger joints, neck and low back.

Cartilage is not the only area affected by Osteoarthritis. Changes occur in all the tissues of the joint, including: subchondral bone, synovium, meniscus, and ligaments.

Even minor joint injuries can cause the progressive loss of cartilage. Ideally, joint pain should be treated soon after it occurs to prevent the joint pain from worsening and progressing to cartilage tears  and arthritis. Hip, knee, and ankle joint damage impairs walking ability, causing reduced activity, decrease in mobility and diminished quality of life.

Once cartilage has been damaged, very few conventional treatments provide relief.

Fortunately, at Oregon Regenerative Medicine, we use an integrated system of nutritional guidance, endocrine support, detoxification, IV Therapy, and adult stem cells to treat osteoarthritis. We use AD-SVF adult stem cells because they are rich in mesenchymal stem cells, which preferentially differentiate into the chondrocytes that form cartilage. By injecting these directly into the damaged joint, your cartilage is given the opportunity to repair itself. Our results show significant improvement in swelling, pain, and mobility in the vast majority of our patients receiving injections directly into their joints.

The treatments described herein are considered experimental and have not been evaluated or approved by the FDA.

Osteoarthritis– A sampling of studies supporting Adipose Derived Stem Cell Therapy:

Biomaterials. 2012 Oct;33(29):7008-18. doi: 10.1016/j.biomaterials.2012.06.058. Epub 2012 Jul 19.

Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration.

Xie X1, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS, Zhang C.

Abstract

The aims of this study were to (1) determine whether platelet-rich plasma (PRP) could be prepared as a bioactive scaffold capable of endogenous growth factor release for cartilage repair; (2) compare the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) from bone marrow (BMSC) and from adipose (ADSC) seeded within the PRP scaffold; and (3) test the efficacy of ADSC-PRP construct in cartilage regeneration in vivo. In vitro evaluation showed that a 3-dimensional scaffold with a mesh-like microstructure was formed from PRP, with the capability of endogenous growth factor release and ready cell incorporation. Upon seeding in the PRP scaffold, BMSC showed higher proliferation rate, and higher expression of cartilage-specific genes and proteins than ADSC. In an osteochondral defect model in rabbits, implanted BMSC seeded within PRP scaffold also exhibited better gross appearance and histological and immunohistochemical characteristics, higher cartilage-specific gene and protein expression as well as subchondral bone regeneration. ADSC seeded constructs developed into functional chondrocytes secreting cartilaginous matrix in rabbits at 9 weeks post-implantation. Our findings suggest that PRP is a candidate bioactive scaffold capable of releasing endogenous growth factors and that BMSC and ADSC seeded within the PRP scaffold differentiate into chondrocytes and may be suitable for cell-based cartilage repair.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22818985 [PubMed – indexed for MEDLINE]

Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells.

Pain Physician. 2008 May-Jun;11(3):343-53.

Centeno CJ1, Busse D, Kisiday J, Keohan C, Freeman M, Karli D.

Abstract

BACKGROUND:

The ability to repair tissue via percutaneous means may allow interventional pain physicians to manage a wide variety of diseases including peripheral joint injuries and osteoarthritis. This review will highlight the developments in cellular medicine that may soon permit interventional pain management physicians to treat a much wider variety of clinical conditions and highlight an interventional case study using these technologies

OBJECTIVE:

To determine if isolated and expanded human autologous mesenchymal stem cells could effectively regenerate cartilage and meniscal tissue when percutaneously injected into knees.

DESIGN:

Case Study

SETTING:

Private Interventional Pain Management practice.

METHODS:

An IRB approved study with a consenting volunteer in which mesenchymal stem cells were isolated and cultured ex-vivo from bone marrow aspiration of the iliac crest. The mesenchymal stem cells were then percutaneously injected into the subject’s knee with MRI proven degenerative joint disease. Pre-and post-treatment subjective visual analog pain scores, physical therapy assessments, and MRIs measured clinical and radiographic changes.

RESULTS:

At 24 weeks post-injection, the patient had statistically significant cartilage and meniscus growth on MRI, as well as increased range of motion and decreased modified VAS pain scores.

CONCLUSION:

The described process of autologous mesenchymal stem cell culture and percutaneous injection into a knee with symptomatic and radiographic degenerative joint disease resulted in significant cartilage growth, decreased pain and increased joint mobility in this patient. This has significant future implications for minimally invasive treatment of osteoarthritis and meniscal injury.

PMID: 18523506 [PubMed – indexed for MEDLINE]

Adipose-derived mesenchymal stem cells for cartilage tissue engineering: State-of-the-art in in vivo studies. J Biomed Mater Res A. 2013 Jul 27. doi: 10.1002/jbm.a.34896.

Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M.

Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute (IOR), 40136, Bologna, Italy.

Abstract

Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose- derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 107 cells for heterotopic cartilage formation and 1 × 106 cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. Copyright © 2013 Wiley Periodicals, Inc.

Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis.

Knee Surg Sports Traumatol Arthrosc. 2013 Dec 11. [Epub ahead of print]

Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE.

Abstract


PURPOSE:
In the present study, the clinical outcomes and second-look arthroscopic findings of intra- articular injection of stem cells with arthroscopic lavage for treatment of elderly patients with knee Osteoarthritis (OA) were evaluated.

METHODS: 
Stem cell injections combined with arthroscopic lavage were administered to 30 elderly patients (≥65 years) with knee OA. Subcutaneous adipose tissue was harvested from both buttocks by liposuction. After stromal vascular fractions were isolated, a mean of 4.04 × 106 stem cells (9.7 % of 4.16 × 107 stromal vascular fraction cells) were prepared and injected in the selected knees of patients after arthroscopic lavage. Outcome measures included the Knee Injury and Osteoarthritis Outcome Scores, visual analog scale, and Lysholm score at preoperative and 3-, 12-, and 2-year follow-up visits. Sixteen patients underwent second-look arthroscopy.

RESULTS:
 Almost all patients showed significant improvement in all clinical outcomes at the final follow- up examination. All clinical results significantly improved at 2-year follow-up compared to 12- month follow-up (P < 0.05). Among elderly patients aged >65 years, only five patients demonstrated worsening of Kellgren-Lawrence grade. On second-look arthroscopy, 87.5 % of elderly patients (14/16) improved or maintained cartilage status at least 2 years postoperatively. Moreover, none of the patients underwent total knee arthroplasty during this 2-year period.

CONCLUSION:
 Adipose-derived Stem Cell Therapy for elderly patients with knee OA was effective in cartilage healing, reducing pain, and improving function. Therefore, Adipose-derived Stem Cell Treatment appears to be a good option for OA treatment in elderly patients.

LEVEL OF EVIDENCE:

Therapeutic case series study, Level IV.
PMID: 24326779 [PubMed – as supplied by publisher]

Cell- and gene-based approaches to tendon regeneration.

J Shoulder Elbow Surg. 2012 Feb;21(2):278-94. doi: 10.1016/j.jse.2011.11.015.

Nixon AJ, Watts AE, Schnabel LV.

Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. ajn1@cornell.edu

Abstract

Repair of rotator cuff tears in experimental models has been significantly improved by the use of enhanced biologic approaches, including platelet-rich plasma, bone marrow aspirate, growth factor supplements, and cell- and gene-modified cell therapy. Despite added complexity, cell- based therapies form an important part of enhanced repair, and combinations of carrier vehicles, growth factors, and implanted cells provide the best opportunity for robust repair. Bone marrow- derived mesenchymal stem cells provide a stimulus for repair in flexor tendons, but application in rotator cuff repair has not shown universally positive results. The use of scaffolds such as platelet-rich plasma, fibrin, and synthetic vehicles and the use of gene priming for stem cell differentiation and local anabolic and anti-inflammatory impact have both provided essential components for enhanced tendon and tendon-to-bone repair in rotator cuff disruption. Application of these research techniques in human rotator cuff injury has generally been limited to autologous platelet-rich plasma, bone marrow concentrate, or bone marrow aspirates combined with scaffold materials. Cultured mesenchymal progenitor therapy and gene-enhanced function have not yet reached clinical trials in humans. Research in several animal species indicates that the concept of gene-primed stem cells, particularly embryonic stem cells, combined with effective culture conditions, transduction with long-term integrating vectors carrying anabolic growth factors, and development of cells conditioned by use of RNA interference gene therapy to resist matrix metalloproteinase degradation, may constitute potential advances in rotator cuff repair. This review summarizes cell- and gene-enhanced cell research for tendon repair and provides future directions for rotator cuff repair using biologic composites.

Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

PMID: 22244071 [PubMed – indexed for MEDLINE]

Chondrogenic potential of stem cells derived from adipose tissue: A powerful pharmacological tool.

Biochem Biophys Res Commun. 2013 Nov 1;440(4):786-91. doi: 10.1016/j.bbrc.2013.10.012. Epub 2013 Oct 14.

Roux C, Pisani DF, Yahia HB, Djedaini M, Beranger GE, Chambard JC, Ambrosetti D, Michiels JF, Breuil V, Ailhaud G, Euller-Ziegler L, Amri EZ.

University Nice Sophia Antipolis, iBV, UMR 7277, 06100 Nice, France; CNRS, iBV, UMR 7277, 06100 Nice, France; Inserm, iBV, U1091, 06100 Nice, France; Service de Rhumatologie, Hospital l’Archet 1 CHU, 06200 Nice, France.

Abstract

Chondrogenesis has been widely investigated in vitro using bone marrow-derived mesenchymal stromal cells (BM-MSCs) or primary chondrocytes. However, their use raises some issues partially circumvented by the availability of Adipose tissue-derived MSCs. Herein; we characterized the chondrogenic potential of human Multipotent Adipose-Derived Stem (hMADS) cells, and their potential use as pharmacological tool. hMADS cells are able to synthesize matrix proteins including COMP, Aggrecan and type II Collagen. Furthermore, hMADS cells express BMP receptors in a similar manner to BM-MSC, and BMP6 treatment of differentiated cells prevents expression of the hypertrophic marker type X Collagen. We tested whether IL-1β and nicotine could impact chondrocyte differentiation. As expected, IL-1β induced ADAMTS-4 gene expression and modulated negatively chondrogenesis while these effects were reverted in the presence of the IL-1 receptor antagonist. Nicotine, at concentrations similar to those observed in blood of smokers, exhibited a dose dependent increase of Aggrecan expression, suggesting an unexpected protective effect of the drug under these conditions. Therefore, hMADS cells represent a valuable tool for the analysis of in vitro chondrocyte differentiation and to screen for potentially interesting pharmacological drugs.

Copyright © 2013 Elsevier Inc. All rights reserved. KEYWORDS:

Chondrocyte, Differentiation, hBM-MSC, hMADS PMID: 24134848 [PubMed – in process] .

Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs.

BMC Vet Res. 2013 Jul 2;9:131. doi: 10.1186/1746-6148-9-131.

Vilar JM, Morales M, Santana A, Spinella G, Rubio M, Cuervo B, Cugat R, Carrillo JM.

Department of Animal Pathology, Faculty of Veterinary Medicine, Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas 35413 Las Palmas, Spain. jvilar@dpat.ulpgc.es

Abstract

BACKGROUND:
 Adipose-derived mesenchymal stem cell (ADMSC) therapy in regenerative medicine is a rapidly growing area of research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify the efficacy of different therapeutic strategies for the treatment of OA in dogs, but never with AD-MSC. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA.

RESULTS:
 Eight lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved after treatment of the OA groups, reaching 53.02% and 14.84% of body weight, respectively, at day 180, compared with only 43.56% and 12.16% at day 0.

CONCLUSION:
This study objectively demonstrated that intraarticular ADMSC therapy resulted in reduced lameness due to OA.

PMID: 23819757 [PubMed – in process] PMCID: PMC3716942

Evidence-based therapy for cartilage lesions in the knee – regenerative treatment options. Z Orthop Unfall. 2012 Jun;150(3):280-9. doi: 10.1055/s-0031-1298387. Epub 2012 Jun 21.

[Article in German]
Proffen B, von Keudell A, Vavken P.

Source

Department of Orthopedic Surgery, Children’s Hospital Boston, Massachusetts, United States.

Abstract

BACKGROUND: 
The treatment of cartilage defects has seen a shift from replacement to regeneration in the last few years. The rationale behind this development is the improvement in the quality-of-care for the growing segment of young patients who are prone to arthroplasty complications because of their specific characteristics – young age, high level of activity, high demand for functionality. These days, two of the most popular regenerative treatments are microfracture and autologous chondrocyte implantation (ACI). Although these new options show promising results, no final algorithm for the treatment of cartilage lesions has been established as yet.

MATERIALS AND METHODS:
 The objective of this review is to describe and compare these two treatment options and to present an evidence-based treatment algorithm for focal cartilage defects.

RESULTS:
 Microfracture is a cost-effective, arthroscopic one-stage procedure, in which by drilling of the subchondral plate, mesenchymal stem cells from the bone marrow migrate into the defect and rebuild the cartilage. ACI is a two-stage procedure in which first chondrocytes are harvested, expanded in cell culture and in a second open procedure reimplanted into the cartilage defect. Microfracture is usually used for focal cartilage defects < 4 cm2, the treated defect size of the ACI seems to have a wider range. The effectiveness of these two treatments has been shown in long-term longitudinal studies, where microfracture showed improvement in up to 95 % of patients, whereas 92 % of the patients in a 2-9 year period of follow-up after ACI showed improvements, respectively. The successful outcome of the treatment depends on multiple factors such as the location of the defect, cell differentiation and proliferation, concomitant problems, and the age of the patient. Associated complications and disadvantages of the two different applications are, for the microfracture patient, a poor tissue differentation or a formation of an intra-lesional osteophyte, and for the ACI patient, periosteal hypertrophy and the need for two procedures in ACI. Only a few studies provide detailed and evidence-based information on a comparative assessment. These studies, however, are showing widely similar clinical outcomes but better histological results for ACI, which are likely to translate into better long-term outcomes.

CONCLUSIONS:
 Although evidence-based studies comparing microfracture and ACI have not found significant differences in the clinical outcome, the literature does show that choosing the treatment based on the size and characteristics of the osteochondral lesion might be beneficial. The American Association of Orthopedic Surgeons suggest that contained lesions < 4 cm2 should be treated by microfracture, lesions bigger than that by ACI.

Georg Thieme Verlag KG Stuttgart · New York.
PMID: 22723070 [PubMed – indexed for MEDLINE]

 

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