Human Umbilical Cord
Mesenchymal Stem Cells
for Rheumatoid Arthritis
Umbilical Cord Tissue-derived Mesenchymal Stem Cells for Rheumatoid Arthritis
Umbilical cord tissue derived mesenchymal stem cells (UC-MSC), are an immune modulatory cell population that has demonstrated therapeutic activity in animal models of autoimmunity [1, 2], as well as clinical trials [3, 4]. Of relevance to rheumatoid arthritis (RA), UC-MSC have been demonstrated to differentiate into bone and cartilage tissue possessing immune privileged properties , as well as inhibit disease onset in models of RA [6, 7].
The proposed trial involves intravenous administration of 100 million UC-MSC in 20 RA patients who have not responded to disease-modifying antirheumatic drugs (DMARDs) in a 6-month period. Subjects will be observed during 52 weeks, with safety and efficacy measurements at 3 and 12 months.
Given the safety record of allogeneic UC-MSC from our internal work, as well as published clinical studies [3, 4, 8-12], we do not anticipate treatment-related serious adverse events. This study will provide support for double-blind placebo controlled investigations. The potential of using a “universal donor” stem cell therapy for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.
- Signed inform consent by the subject.
- Age older than 18 years and ability to understand the planned treatment.
- Patients of either gender with RA with a duration of 6 to 72 months defined as the presence of at least three of the following criteria: 6 or more painful, 2 or more swollen joints, morning stiffness for at least 45 minutes (on average during the week prior to entry), and an erythrocyte sedimentation rate (ESR) of at least 28 mm.
- Non-responsive to at least one course of one DMARD selected from the group comprising of: gold salts, leflunomide, methotrexate, and hydroxychloroquine.
- Second-line agents are discontinued at least 4 weeks prior to entry.
- Able to tolerate ALL study procedures
- Able to give informed Consent
- Negative for HcG with a serum pregnancy test
- Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000,
- Life expectancy of 6 months or more in the opinion of the investigator
- Serum bilirubin, ALT, AST up to 2.5 time the upper level of normal.
- Controlled blood pressure (systolic blood pressure ≤140 and a diastolic blood pressure of ≤90 mmHG) and established anti-hypertensive therapy as necessary prior to entry into the study
- Patient has received stable, standard medical therapy for at least one month with no new medications to treat the disease introduced in the last month.
- Pre-existing condition (e.g. thromboembolic risk, diabetes, hypercholesterolemia) are adequately controlled in the opinion of the investigator
- Fertile patients (male and female) must agree to use an appropriate form of contraception while participating in the study.
- Female who is pregnant or nursing, or of child-bearing potential and is not using a reliable birth control method, or who intend to become pregnant during the tenure of this study.
- History of prior radiation exposure for oncological treatment.
- History of Bone Marrow Disorder (especially NHL, MDS)
- History of abnormal bleeding or clotting.
- History of Liver Cirrhosis.
- End stage renal disease (Creatinine ≤ 3.0 mg / dl) and/or dialysis
- Active clinical infection being treated by antibiotics before one week enrollment
- Inability or unwillingness to comply with the treatment protocol, follow-up, research tests, or give consent.
- History of life-threatening arrhythmias, except if an automated implantable cardioverter defibrillator (AICD) is implanted
- Life expectancy <6 months due to concomitant illnesses
- Known cancer and undergoing treatment; chemotherapy and/or radiotherapy
- Patients receiving treatment with hematopoietic growth factors (e.g., EPO, G-CSF)
- Patients who can not stop anticoagulation therapy (warfarin) 72hrs prior to infusion
- Patients who can not stop anti-platelet therapy (clopidogrel) 7 days prior infusion
- Prior admission for substance abuse
- Body Mass Index (BMI) of 40 kg/m2 or greater
- Patient receiving experimental medication or participating in another clinical study within 30 days of signing the informed consent
- In the opinion of the investigator or the sponsor, the patient is unsuitable for cellular therapy
- Anzalone, R., et al., Wharton’s jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes. Stem Cell Rev, 2011. 7(2): p. 342-63.
- Liu, R., et al., Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev, 2013. 22(7): p. 1053-62.
- Hu, J., et al., Long term effects of the implantation of Wharton’s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J, 2013. 60(3): p. 347-57.
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- Wu, K.H., et al., Cotransplantation of umbilical cord-derived mesenchymal stem cells promote hematopoietic engraftment in cord blood transplantation: a pilot study. Transplantation, 2013. 95(5): p. 773-7.
- Wu, K.H., et al., Human Application of Ex-Vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation. Cell Transplant, 2013.
- Liang, J., et al., Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler, 2009. 15(5): p. 644-6.
- Zhang, Z., et al., Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol, 2012. 27 Suppl 2: p. 112-20.