ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autologous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoimmune diseases.</p><p><b>METHODS</b>Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored.</p><p><b>RESULTS</b>Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and another of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.</p><p><b>CONCLUSION</b>HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Antigens, CD34 , Arthritis, Rheumatoid , Allergy and Immunology , Therapeutics , Autoimmune Diseases , Allergy and Immunology , Therapeutics , Cyclophosphamide , Therapeutic Uses , Dose-Response Relationship, Drug , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents , Therapeutic Uses , Lupus Erythematosus, Systemic , Allergy and Immunology , Therapeutics , Pilot Projects , Recurrence , Sjogren's Syndrome , Allergy and Immunology , Therapeutics , Transplantation Conditioning , Transplantation, AutologousABSTRACT
Human mesenchymal stem cells (MSC) are one kind of adult stem cells that can self-renew and give rise to one or more mesenchymal tissues, existing in bone marrow and other tissues. Not similar to CD34 recognizing hematopoietic stem cells, no such marker can be used yet to identify MSC. To isolate and identify MSC from bone marrow, anti-SH2 and SH3 monoclonal antibodies as markers to identify MSC were used. Two monoclonal antibodies were purified from ascites of SH2 and SH3 hybridomas-inoculated mice, flow cytometry and immunohistochemistry were used to identify plastic-adherent cultured MSC. And SH2 and SH3 antigen positive cells were isolated from bone marrow mononuclear cells (BMMNC) by immunobeads covered with secondary antibodies. And anti-SH2 and CD105 McAbs were used to label MSC at the same time to clarify whether they recognize the same antigen. The results showed that about 80% of MSC were antigens SH3 and SH2 positive. The SH2 and SH3 positive-selected cells were MSC while MSC accounted for less than 1% of negative-selected cells. When cells were labeled by SH2 McAb, they could not be labeled by CD105 simutaneously. In conclusion, antigens SH2 and SH3 are specific markers to identify and isolate MSC. Anti-SH2 McAb can replace anti-CD105 McAb to identify the specific marker on MSC.