Case 1
A 16-year-old female with SLE initially presented at the age of 9 years with the sole symptom of idiopathic scleritis requiring steroid eye drops intermittently for flares. After 3 years into her illness, she developed polymyositis with severe arthritis with elevated muscle enzymes, speckled antinuclear antibody (ANA) of 1:640, and negative lupus serologies for double stranded (ds)DNA and extractable nuclear antigen (ENA). She was diagnosed with undifferentiated connective tissue disease (UCTD) and started on methotrexate and meloxicam with minimal efficacy.
In the next nine months, she progressed to develop a malar rash and sustained leukopenia and lymphopenia. Her diagnosis was subsequently refined to SLE, meeting American College of Rheumatology 1997 revised criteria with malar rash, arthritis, positive ANA, and hematologic abnormalities. Her treatment included hydroxychloroquine and prednisone followed by disease-modifying anti-rheumatic drugs (DMARDs) and biologics as steroid-sparing medications including methotrexate, leflunomide, abatacept, tocilizumab and azathioprine over the following 48 months with limited efficacy. She continued to have recurrent scleritis and active arthritis causing significant pain.
After consultation with a company in Texas, Celltex, the patient and her family made the decision to travel to Cancun, Mexico for autologous adipose tissue-derived MSC transplantation. The cells were harvested from abdominal adipose tissue by liposuction in California, sent to Celltex for MSC isolation and preparation for transplant that was infused in a clinic in Cancun, Mexico. She received one intranasal injection (100 × 106 cells), one lymph node injection (100 × 106 cells), three intravenous transfusions (379 × 106, 256 × 106, and 393 × 106 cells) given within one week, then one further intravenous transfusion (234 × 106 cells) nine months later. The target dose per treatment was 200 × 106 cells (3.3 × 106 MSCs/kg/dose). While she was on MSC treatment, all conventional immunosuppressive medications were discontinued. After receiving MSC transplantation, she had a transient flare with arthralgia, malar rash, and recurrence of scleritis, which subsequently resolved in 2 months without treatment. Otherwise, she had no other minor or serious adverse effect from MSC transplantation. During 18 months follow-up since MSC, she remains clinically stable; patient global assessment (PGA) decreased from 8/10 to 1/10 after treatment and physician global assessment from 7/10 to 2/10. The ANA titer declined from 1:640 to 1:80–160. Currently, she is only on intermittent topical ocular prednisolone therapy for rare patient-reported scleritis episodes and continues to have regular visits to pediatric rheumatology and ophthalmology clinics for routine monitoring.
Case 2
A 19-year-old female was diagnosed with MCTD consisting of SLE and systemic sclerosis features at age of 15 years. Initial presentation included intermittent fevers, Raynaud’s phenomenon, cervical lymphadenopathy, arthritis in her wrist and hips, generalized fatigue, weakness, dyspnea, and photosensitivity. Laboratory evaluation revealed high titer ANA (> 1:1280, Speckled), positive serologies for dsDNA and ribonucleoprotein antibodies and positive rheumatoid factor (RF). Ultrasound-guided lymph node biopsy showed benign reactive lymphadenopathy; no malignant cells or infectious organisms were identified. She was treated with multiple DMARDs and biologics including methotrexate, hydroxychloroquine, leflunomide, mycophenolate mofetil, rituximab, abatacept, and belimumab. She remained on intermittent low to moderate dose oral prednisone throughout this time. Her response to treatment was marginal; her annual pulmonary function studies showed gradual reduction in diffusing capacity for carbon monoxide (DLCO) down to 41.5% predicted, although her high-resolution chest computed tomography and repeat echocardiograms remained normal.
Three years into her treatment, she developed significant pain and weakness. She was admitted and treated for polymyositis. Magnetic resonance imaging (MRI) revealed avascular necrosis of both hips. She was started on tocilizumab and received four doses administered intravenously every 14 days with improvement. Due to poor quality of life from hip pain, she pursued MSC treatment locally at AMA Regenerative Medicine & Skincare. The MSC were derived from Wharton’s jelly after a cesarean birth and processed under a strict procedure by Vitti Labs (a Food and Drug Administration-registered tissue bank) to ensure viability, non-infectivity, and lack of genetic mutations. She received MSCs via intravenous transfusion as well as intraosseous injections directly into the head of the femurs bilaterally. Three hip injections (1 cc of Wharton’s Jelly MSC; 1.1 × 106 MSCs) were given at months 0, 2, and 6, while intravenous transfusions (60 × 106 MSCs; 1.2 × 106 MSCs/kg/dose) were given at months 2 and 6. She continued on twice monthly intravenous tocilizumab during the first 2 months of MSC treatment; all conventional immunomodulatory therapy was discontinued thereafter. The patient reported fatigue and local pain at the site of the hip injections for three days but did not have any minor or serious adverse effect. Patient reported an improvement with a pre-treatment PGA of 7/10 and post-treatment PGA of 2/10. She had previously dropped out of her college semester pre-transplant and was able to return to full time studies and dance. Although her serologies remained unchanged, the erythrocyte sedimentation rate (ESR) normalized for 3 months after initial MSC therapy and remains only mildly elevated compared to pre-treatment levels. Although there continues to be radiographic evidence of avascular necrosis of the hips, there has been no collapse of the femoral head and the scheduled bilateral hip replacement surgery has been cancelled.
Case 3
An 18-year-old female with diagnosis of RF positive and HLA B27 positive JIA presented initially at 11 years of age with right knee arthritis, then progressed to arthritis in bilateral knees, left elbow, and cervical spine. Her arthritis activity correlated with increased ESR. Treatment included non-steroidal anti-inflammatory drugs (naproxen, sulindac, meloxicam), followed by methotrexate (initially oral, then subcutaneous). Incidentally, she also had thoracic outlet syndrome causing neck pain and right arm paresthesia during dirt bike racing. For two years, she transferred her care to another institution, where she began etanercept with methotrexate. She had a brief remission three years into her initial diagnosis. A routine MRI of her elbow then showed active synovitis and new erosions, which led to a recommendation to switch to another biologic therapy. However, severe localized pain with biologic injections prompted the family to explore stem cell therapy abroad. She transferred back to our institution due to disagreement about MSC therapy with the outside institution. Her PGA prior to MSC treatment was 6/10.
She underwent an umbilical cord MSC transplant at Stem Cell Institute in Panama at the age of 16 years old. The transplant involved three intravenous infusions over four days with cells derived from donor human umbilical cord tissue-derived MSC (120 × 106 MSCs; 1.8 × 106 MSCs/kg/dose). The transplant physicians instructed the patient to wean off her rheumatic medications prior to the transfusion. She had no initial side effects, though developed a migratory arthritis flare 5 weeks post-transplantation, that was attributed to a Jarisch-Herxheimer reaction. No other minor or serious adverse effects were reported.
An MRI of her left elbow 5 months post-transplantation revealed continued active synovitis and progression of erosive changes. Post-transplantation labs remained unchanged with positive RF, as well as positive anti-cyclic citrullinated peptide antibodies, but there was a normalization of ESR. A biologic medication was prescribed but never taken by the patient. She was maintained on celecoxib therapy in the interim. One year after her initial transplant, she returned to Panama for a second MSC intravenous transfusion (120.6 × 106 cells; 1.9 × 106 MSCs/kg/dose). She developed flu-like symptoms with this treatment. Follow-up 3 months later showed worsening elbow contracture and active synovitis on MRI, though no worsening of erosions. She had an intra-articular steroid injection to the elbow joint the following month with marked improvement in her symptoms. Family decided to initiate a complement of holistic management including monthly hyperbaric oxygen, red-light therapy with in-home lymphatic draining twice weekly, and daily pulsed electromagnetic field therapy. Her most recent PGA is 1/10 and the family is content with her current condition.