• Incidence rate of biopsy-proven acute rejection [ Time Frame: At 1 year post-transplant ] [ Designated as safety issue: Yes ]
  

• Patient and graft survival [ Time Frame: At 1 year post-transplant ] [ Designated as safety issue: Yes ]
  

Renal transplantation is the most common and successful type of organ transplantation. Much progress in the survival of the grafted kidney has been made in the previous 2 decades, especially since the introduction of immunosuppression agents. New immunosuppressive agents, such as cyclosporine (CsA), FK506 and mycophenolate mofetil (MMF), can obviously decrease the acute rejection of transplanted kidney, and improve both the short-term and long-term organ survival. However, at the present time, acute rejection still occurs and chronic rejection is the most common cause of late graft loss.

Mesenchymal stem cells(MSCs), or marrow stromal cells, are multipotential cells that reside within the bone marrow and can be induced to differentiate into various components of the marrow microenvironment, such as bone, adipose and stromal tissues under proper conditions. It has been reported that MSCs can suppress maturation, activation and proliferation of T, B, NK and DC cell in vitro and downregulate immune response in vivo. MSCs are presently being cotransplanted with hematopoietic stem cell, which can facilitates engraftment of hematopoietic stem cells and prevent GVHD. Most importantly there is clear evidence that therapy with MSCs affords significant renal protection in rats with ischemic/reperfusion acute renal failure. Animals infused with MSCs either immediately or 24 hours after reperfusion had significantly better renal function, lower renal injury and cell-death scores, and higher cell division indices than vehicle-treated control animals.

In this study we will co-transplant autologous MSCs with kidney allograft to further suppress immune rejection and improve donor kidney survival. For this purpose some patients in this study will receive two infusions of MSCs harvested from their bone marrow. Safety and effectiveness of MSCs infusions in patients undergoing kidney transplantation will be evaluated.

This study will enroll 60 patients with end-stage renal disease. Participants will be randomly assigned to receive either the standard immunosuppressive therapy of our institute and autologous MSCs infusions (Group A) or standard immunosuppressive therapy alone (Group B). Patients will undergo kidney transplantation at the start of the study (Day 0). Patients in Group A will receive the first MSCs infusion intravenously within 24 hours and another infusion two weeks post-transplant, respectively.

Inclusion Criteria:

• Patients must be between the ages of 18 and 60 years and meet the institution's criteria for renal transplantation for end-stage renal failure
• Patient is receiving the first renal transplant
• Patient is receiving a renal transplant only
• Women who are of child bearing potential must have a negative pregnancy test (urine test is acceptable) and agree to use reliable contraception for 1 year following transplant
• Willing to comply with the study visits
• Be able to sign informed consent document.

Note: The subjects do not need to be local residents in order to be eligible for this trial, but must be willing to reside in the area, or within a four hour drive, for the first three months of the protocol so that we can monitor them closely in the early post transplant period.

Exclusion Criteria:

• Previously received or is receiving an organ transplant other than a kidney
• Significant liver disease, defined as having continuously elevated AST (SGOT) or ALT (SGPT) levels greater than 3 times the upper value of the normal range within 28 days prior to study entry
• HIV infection.
• Surface antigen positive for HBV.
• Antibody positive for hepatitis C virus
• Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB
• Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant.
• Currently receiving any immunosuppressive agent.
• Clinically active bacterial, fungal, viral or parasitic infection
• Evidence for immunologic memory against donor.
• Recipients need antibody induction treatment before the operation.
• Current cancer or a history of cancer within the 5 years prior to study entry.
• Serious heart and lung diseases.
• Patients who's RPR is positive
• Pregnancy or breastfeeding.
• Have no ability to communicate.
• Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study