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Ankylosing spondylitis, chronic fatigue and depression improvements: a case report

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Ankylosing spondylitis, chronic fatigue and depression improvements: a case report

August 30,2018

Macquarie Stem Cells has provided this information to educate the public based on peer reviewed, published scientific and medical documents. We don’t aim to encourage consumers to seek out such treatments prior to an assessment by a health professional to determine your suitability for treatment. This is obtained directly from BMC Journal of Medical Case Reports. This study was privately funded by the patient. We aim to provide you with an unbiased range of treatments that are available aside from biological therapy, This is discussed in ‘other-options’  page on our website.

TITLE: Ankylosing spondylitis, chronic fatigue and depression improved after stromal vascular fraction treatment for osteoarthritis: a case report(Bright et al., 2018)

Published: 29th Aug 2018
Authors: Bora Bright, Dr. Ralph Bright, Pelin Bright, Dr. Amita Limaye
BMC Journal of Medical Case Reports

Abstract

Background: “Osteoarthritis (OA) is a prevalent chronic disease impacting quality of life and posing a heavy economic burden. Despite this there is no confirmed treatment that could prevent progressive destruction of OA joints. Mesenchymal stem cells with their regenerative and immunosuppressive properties have emerged as a potential therapy.”(Bright et al., 2018)

Case Presentation: “This case study describes the impact of autologous adipose derived stromal vascular fraction (SVF) treatment on osteoarthritis patient, including multiple comorbidities of ankylosing spondylitis (AS) chronic pain syndrome, and post-traumatic stress disorder as assessed by Magnetic Resonance Imaging (MRI) Western Ontario Universities Osteoarthritis Index (WOMAC) and Hip Disability and Osteoarthritis Outcome Score (HOOS). Following standardized SVF treatment protocols for osteoarthritis of the hips and knee, the patient’s functional status of the hips was measured by HOOS at 3 months, 6 months and 3 years.”(Bright et al., 2018)

Conclusions: “The patient showed dramatic improvements to her quality of life and symptoms of osteoarthritis were reduced. Interestingly, along with improvements of her knee and hips her other co-morbidities such as AS, depression, anxiety and fatigue exhibited marked improvement. The patient ceased the use of wheel chair and walking support, and with increased mobility had gained independence. Thereby suggestive of therapeutic effects of effect of SVF.”(Bright et al., 2018)

Complete Publication can be found below.

Background

“Osteoarthritis (OA) is characterised by degeneration of articular cartilage, sclerosis of the subchondral bone and marginal osteophyte formation. OA is associated with chronic pain, stiffness, decreased range of motion and joint deformity, muscle wasting and tendonitis. The diagnosis of OA relies on clinical symptoms, physical findings, and radiographic findings. Often discordance is found between radiological findings and symptomatic findings of OA 1.  The aetiology of OA appears to be multifactorial with hereditary, metabolic, hormonal, developmental and mechanical components 2.  Apart from mechanical and genetic factors that contribute to development of OA, age has been a primary risk factor 3. Age associated changes in cartilage extra-cellular matrix, increase in inflammatory cytokine milieu locally and of increased free radical species have been implicated in loss of ability of cartilage to adapt to mechanical stress or load 4. Interestingly depletion of the mesenchymal stem cells in local stromal population has been indicated to be associated with OA 5,6. Whether it is a cause or an effect of OA remains to be elucidated. Current treatments include lifestyle modifications and diet together with pain relief using paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) in early OA. However, the advanced disease relies on total joint replacement which is found to be associated with complications. Lifespan of prosthesis is limited so surgery is delayed until symptoms are limiting the lifestyle and is avoided in younger patients. Since most of the above mention modalities only provide symptomatic relief, the regenerative potential of stem cells to repair injured and damaged tissue is a promising new strategy in the field of orthopaedics. Of these options, patient derived (autologous) minimally manipulated, mesenchymal stem cells, for treatment of chronic diseases such as OA is being investigated to achieve clinical significance 7.”(Bright et al., 2018)

“Here we describe a case report on the healing effect of adipose derived stromal vascular fraction in a female with X-ray, MRI, CT-scan and ultrasound scan confirming peripheral spondyloarthritis, Sacroilitis Grade II, Enthesitis and Ankyosing spondylitis. Ankylosing spondylitis (AS) is a form of arthritis that primarily impacts the spine, causing inflammation, leading to chronic pain. AS symptoms often includes disturbances of sleep, fatigue, depression and anxiety 8, thereby profoundly impacting upon the patient’s quality of life. AS is predominantly detected in patients between the ages of 20 and 40 years and can be triggered by multiple factors that are similar to OA. Conditions associated with inflammation such as OA and AS are controlled by non-steroidal anti-inflammatory drugs (NSAIDs) and common analgesic medication 9.”(Bright et al., 2018)

“Mesenchymal Stem Cells (MSC) can be found throughout the body. Adipose tissue is an excellent source of stem cells having 10-100 times more MSCs than bone marrow 10. Stromal vascular fraction (SVF) can be easily obtained from loose connective tissue that is associated with adipose tissue by process of liposuction under local anaesthesia. SVF is a collection of heterogeneous population of MSC, HSC, Treg, pericyte-EC, mast-cells, complex microvascular structure (fibroblasts, WBC, DCs, intra-adventitial smooth muscle-like cells) and ECM. The immunomodulatory, anti-inflammatory and regenerative properties of SVF are not attributed to a single type of population residing within albeit it is an effect of all the types of cells constituting the SVF. The use of SVF as a medical treatment is increasing due to the abundance of its cellular properties, ease of collection, immunomodulatory properties and safety 11.”(Bright et al., 2018)

“The aim of this treatment was to reduce pain associated with OA and improve the patient’s quality of life without the need for NSAIDs or analgesics. The patient was expected to show significant improvements in her OA, along with some minor improvements to general inflammation present within her body. Interestingly, short term follow-up presented improvements in her OA as well as comorbidities of AS, depression, anxiety and fatigue. A 3 year follow up including multiple injections of SVF indicated significant changes in patient’s quality of life. All conditions maintained their improvements at the follow-up intervals. Final follow up occurred in June 2017.”(Bright et al., 2018)

Case presentation

“The patient was a 27 years old female with confirmed X-ray images of her pelvis indicated grade IV osteoarthritis; ultrasound scans showed right knee joint effusion, enthesitis and synovitis; CT scan of the spine indicated annulus bulges at L3/4, L4/5 and bilateral grade 2 sacroiliitis changes and a background of ankylosing spondylitis (HLAB-27 negative) confirmed by MRI imaging, chronic pain syndrome with pain amplification and post-traumatic stress disorder. Her BMI was 39.4 kg/m2. The patient did not have any infection with hepatitis B, C or HIV, any malignancy, any previous history of allergic reaction to any component of our therapeutic measure, any active cardiac, respiratory, neurologic or endocrine disease necessitating receipt of medication and was not pregnant or in lactating condition. A written and informed consent was obtained from the patient.   Arthritic symptoms were measured using WOMAC and HOOS by scoring for pain intensity, walking ability (distance), joint stiffness, physical function, sports and recreation and quality of life. The patients AS symptom changes were measured using the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). For liposuction and stem cell treatment, patient was admitted to Macquarie Stem Cells. Under light sedation and using aseptic technique 450ml of fat was harvested from abdomen. Cell isolation was performed in PC II safety cabinet. Cells were isolated using Collagenase digestion using Liberase (GMP grade).”(Bright et al., 2018)

The patient’s pre-operative HOOS score (baseline score) for both hips was 122 (Range 0 – 168), WOMAC for her right knee was 70 (Range 0 – 90). and the baseline ASQoL questionnaire was 18 (Range 0 – 18). 2.058 billion nucleated cells with a viability of 89.10% were obtained using Muse® Cell Analyzer. A total of 738 million cells were injected on the day. With 100 million cells injected into each hip and right knee intra-articular under ultrasound guidance and 438 million cells were administered as an IV infusion. The remaining 1.320 billion cells were cryogenically frozen into 4 separate vials of 330 million cells following the protocols of Thirumala et al., 12. Follow up IV infusions of 330 million cells were provided at 3 months, 12 months and 36 months each.  Patient follow up intervals were at performed at 1 day, 3 months, 6 months, 12 months, 24 months and 36 months respectively. Neither local nor systemic adverse events were observed during the follow-up and the patient was satisfied with the therapy after three months with an increasing trend over the period. At 3 months post treatment, the patient exhibited increased mobility. Her HOOS and WOMAC score decreased to 82 and 37 respectively from her baseline scores. Patient also noted that pain in her spine, hips and right knee associated with OA and AS had decreased. Interestingly accompanied with her decreased pain and increased mobility the patient was feeling more energetic.  Within 6 months post first SVF infusion, patient’s HOOS and WOMAC questionnaire scores had decreased to 79 and 31 respectively. Patient showed dramatic improvements over 2 years past her first SVF infusion and presented with decreased dependency on wheel chair or walking stick (HOOS and WOMAC score not available). The patient’s dependency on pain relief and anti-depressant medications was found to be decreased as is evident from Table 1 (supplementary data available on BMC website). At the 36 months follow up, patient presented significant improvements overall. Patient remained free from NSAIDs and her pain levels were minimal. Follow up HOOS and WOMAC scores had decreased 32 and 20 respectively. Her pre to post treatment ASQoL score has decreased to 3 signifying increased quality of life. She still presents some symptoms of depression however her anxiety appears to have resolved almost completely. Patient’s progressive improvement is observed over 3 years with WOMAC, HOOS and ASQoL (Figure 1a and 1b)”(Bright et al., 2018)

Discussion and Conclusion

“Consistent with our findings, positive therapeutic effects of SVF have been shown in treatment of osteoarthritis of hip and knee 7. In 2011 case series of 339 patients treated with SVF, Centeno et al., reported that 69% of patients were candidates for knee replacement. However, after treatment with MSC’s only 6.9% took up the option for replacement. Sixty percent of patients reported >50% pain relief and 40% reported >75% pain relief at 11 months 13.  We report here, that SVF infusion given via IV as well as IA was not only safe but effective in alleviating the pain associated with Grade IV OA of hips and knee. HOOS and WOMAC scores showed 73% improvement over baseline (Figure 2). HOOS & WOMAC questionnaires are both subjective measurements used to observe function following joint arthroscopy and arthroplasty procedures and are proven to be useful for the evaluation of patient relevant outcomes 14.  Interestingly, her AS also showed improvements based on AS quality of life score. Her ASQoL score decreased from 18 down to 3 post SVF treatment.  Assessing the patient’s ankylosing spondylitis utilised the ASQoL questionnaire, a feasible method of determining the patient’s quality of life 15.”(Bright et al., 2018)

“This is a first study reporting improvement of AS a co-morbidity along with OA. In 2014, Wang et al. conducted the ASAS20 study, which involved treating AS patients via IV infusion of allogeneic cells with a 20 week follow up. The findings confirmed improvements via both objective MRI evaluations as well as subjective questionnaires. The responders showed 77.4% improvements based on the questionnaire assessment, and the MRI reports confirmed a decrease of inflammation 16. These result, are similar to the findings of the study observed here, except the use of allogeneic bone marrow derived stem cells.  Allogeneic and autologous cells are similar in nature, however previous publications have shown autologous cells can be better in performance and safety when compared to allogeneic cells 17,18.  SVF contains a high number of ASC’s that are reported to preferentially migrate towards injured, inflamed or hypoxic tissues to promote regeneration 19. Chemokines and cytokines play an important role in cell activation, survival and differentiation as well as cell migration. Inflammation is a key biomarker in driving depression 20,21. SVF plays a key role in suppressing inflammation, thereby aids in repair and regeneration. Medications such as Lyrica, Nexium and Orudis have been associated with minor side effects of depression. We need to consider that possible reasons for improved depression could be related to decrease in medication use, along with the immunomodulatory effects of SVF. The hypothesis in improving patient’s quality of life is not only due to improvements in arthritic changes, it can also be associated due to suppressing the inflammatory biomarkers that are linked to depression. This original case report provides insight into the fact that SVF treatment has potential to improve patients’ quality of life by improving joint function and mobility, decreased pain in patients with OA as well as AS.    Further study utilising multiple patients is required to conclude the effectiveness of this treatment for AS.”(Bright et al., 2018)

 

REF: Bright, B., Bright, R., Bright, P. and Limaye, A. (2018). Ankylosing spondylitis, chronic fatigue and depression improved after stromal vascular fraction treatment for osteoarthritis: a case report. Journal of Medical Case Reports, 12(1).

TAGS: Macquarie Stem Cells, Possibilities of Biological Treatments, Focusing on Osteoarthritis, Macquarie Stem Cells treating osteoarthritis, Dr. Ralph Bright biological treatment, Bora Bright publication, BMC Journal, Medical Case Reports

 

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