Tolerance by Engaging Antigen During Cellular Homeostasis

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study was to determine if: * it was safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and * the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs could allow a kidney transplant recipient to slowly reduce and/or then completely stop all anti-rejection drugs, without rejection of their kidney (renal) allograft, a process called "immunosuppression withdrawal".

Inclusion Criteria: Recipient: * Adult candidates of an human leukocyte antigen (HLA)-non-identical, living-donor kidney transplant: --Candidates had to meet the United Network for Organ Sharing (UNOS) criteria, including laboratory criteria, for transplant listing; * Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing; * Serological evidence of prior Cytomegalovirus (CMV) infection if donor was CMV positive; * For women of child bearing potential: * A negative serum or urine pregnancy test with sensitivity of less than 50 mIU/mL within 72 hours of start of study medication; and * Agreement to use contraception: * According to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there were a number of birth control methods that were more than 80% effective * Female recipients of child-bearing potential had to consult with their physician and determine the most suitable method(s) from this list to be used for 18 months after the first dose of study therapy. Donor: * Met institutional selection criteria for organ and bone marrow donation: --All donors were screened and tested in accordance with: * (i) FDA 21 CRF 1271.85 requirements for donors of human cells, tissues, and cellular- and tissue-based products (HCT/P); and * (ii) standards for living kidney donors testing for infection established by the United Network for Organ Sharing (UNOS). Ability to understand and provide informed consent for all study procedures including kidney transplant and bone marrow harvest. Exclusion Criteria: Recipient: * History of any immunodeficiency syndrome (including Human Immunodeficiency Virus-1 (HIV-1) and HIV-2); * Positive anti-Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR), anti-Hepatitis C Virus (HBV) PCR, or HBV surface antigen; * History of malignancy within 5 years of enrollment or any history of hematogenous malignancy or lymphoma; --Exception: Participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ could be enrolled. * Underlying renal disease with high likelihood of recurrence, including but not limited to: * primary focal segmental glomerulosclerosis (FSGS), * Type I or II membranoproliferative glomerulonephritis (MPGN), * hemolytic-uremic syndrome and * thrombotic thrombocytopenic purpura (HUS/TTP) syndrome. ---Subject(s) with end-stage renal disease (ESRD) of unknown etiology and/or who had no histologically confirmed diagnosis, could be enrolled into the study as long as there were no clinical signs or symptoms consistent with excluded clinical diagnoses. * History of active M. tuberculosis: --Participants with a history of latent M. tuberculosis (LTB) as defined by positive testing for tuberculosis using an approved IGRA blood test, such as QuantiFERON®-Gold TB or T-SPOT-TB assay had to: * have completed treatment for LTB and * have a negative chest x-ray. ----All participants underwent IGRA testing for M tuberculosis within 3 months prior to transplant. * Current or historical evidence of donor-specific antibody; * Immunosuppressive drug therapy within one year prior to enrollment. * May not have been taking or have taken prednisone, cyclosporine A, tacrolimus, azathioprine, Mycophenolate Mofetil (MMF), cyclophosphamide, methotrexate, infliximab, etanercept, or other agents which had a primary therapeutic effect of immunosuppression in the year prior to transplantation. * May not have taken depletional anti-lymphocyte agents at any time. ---Exceptions: * Short (≤ 30 days) courses of topical or inhaled steroids were permitted, as were * Short oral or parental pulses for a documented hypersensitivity reaction. * Active autoimmune disease requiring ongoing immunosuppressive therapy or other conditions in which there was an anticipated need for immunosuppressive maintenance therapy; * Uncompensated congestive heart failure, pulmonary edema, or symptomatic pulmonary hypertension; * Active severe infection within a month of the screening visit; * Use of an investigational drug within 30 days of the screening visit; * Presence of any medical condition that the investigator deemed incompatible with trial participation; or * Inability or unwillingness to comply with protocol monitoring and therapy. Donor: * History of blood donation to the recipient; * Evidence of prior Cytomegalovirus (CMV) infection if the recipient was CMV negative; * History of HIV-1/HIV-2 infection; * Positive HCV PCR, HBV PCR or HBV surface antigen; or * Presence of any medical condition that the investigator deemed incompatible with trial participation.