EX-VIVO EXPANSION OF HEMATOPOIETIC-CELLS AND THEIR CLINICAL USE

Background and Objective. Hematopoietic stem cells are being increasin gly used for treatment of malignant and nonmalignant disorders. Variou s attempts have been made in recent years to expand and manipulate the se cells in order to increase their therapeutic potential. A Working G roup on Hematopoietic Cells has analyzed the most recent advances in t his field. Evidence and Information Sources. The method used for prepa ring this review was an informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to achieve an agreement on diffe rent judgments, and eventually approved the final manuscript. Some aut hors of the present review have been working in the field of stem cell biology, processing and transplantation, and have contributed origina l papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in jo urnals covered by the Science Citation Index(R) and Medline(R). State of Art. Over the last decade, recombinant DNA technology has allowed t he large scale production of cytokines controlling the proliferation a nd differentiation of hemo-lymphopoietic cells. Thus, in principle, ex vivo manipulation of hemopoiesis has become feasible. The present rev iew covers three major area of interest in experimental and clinical h ematology: manipulation of hematopoietic stem/progenitor cells, cytoto xic effector cells and antigen presenting dendritic cells. Preliminary data demonstrate the possibility of using, in a clinical setting, ex vivo expanded hematopoietic cells with the aim of reducing, and perhap s abrogating, the myelosuppression after high-dose chemotherapy. Concu rrently, other important potential applications for ex vivo manipulati on of hematopoietic cells have recently been investigated such as the generation and expansion of cytotoxic cells for cancer immunotherapy, and the large scale production of professional antigen presenting cell s capable of initiating the process of immune response. Conclusions an d Perspectives. Present and future challenges in this field are repres ented by the expansion of true human stem cells without maturation, to extend this strategy to allogeneic stem cell transplantation as well as the manipulation of cycling of primitive progenitors for gene thera py programs. The selective outgrowth of normal progenitor cells over n eoplastic cells to achieve tumor-free autografts may ameliorate the re sults of autologous transplantation. The selective production of cellu lar subsets to manipulate the graft versus-host and graft versus-tumor effects and anti-tumor vaccination strategies may be important to imp rove cellular adoptive immunotherapy. (C)1998, Ferrata Storti Foundati on.