Human Umbilical Cord
Mesenchymal Stem Cells
for Rheumatoid Arthritis

 

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This trial is no longer recruiting subjects.

Umbilical Cord Tissue-derived Mesenchymal Stem Cells for Rheumatoid Arthritis

Abstract

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 [5], 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.

Inclusion Criteria

  • 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.

 

Exclusion Criteria

  • 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

As seen on ClinicalTrials.gov

View this clinical trial on National Institutes of Health ClinicalTrials.gov

References

  1. 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.
  2. 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.
  3. 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.
  4. Ma, L., et al., Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients. Thromb Haemost, 2012. 107(5): p. 937-50.
  5. La Rocca, G., et al., Human Wharton’s jelly mesenchymal stem cells maintain the expression of key immunomodulatory molecules when subjected to osteogenic, adipogenic and chondrogenic differentiation in vitro: new perspectives for cellular therapy. Curr Stem Cell Res Ther, 2013. 8(1): p. 100-13.
  6. Liu, Y., et al., Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther, 2010. 12(6): p. R210.
  7. Greish, S., et al., Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model. World J Stem Cells, 2012. 4(10): p. 101-9.
  8. Shi, M., et al., Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med, 2012. 1(10): p. 725-31.
  9. 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.
  10. 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.
  11. Liang, J., et al., Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler, 2009. 15(5): p. 644-6.
  12. 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.