Ex vivo expansion of hematopoietic cells and their clinical use

Background and Objective. Hematopoietic stem cells are being increasingly used for treatment of malignant and nonmalignant disorders. Various attempts have been made in recent years to expand and manipulate these cells in order to increase their therapeutic potential. A Working Group on Hematopoietic Cells has analyzed the most recent advances in this field. Evidence and Information Sources. The method used for preparing 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 different judgments, and eventually approved the final manuscript. Some authors of the present review have been working in the field of stem cell biology, processing and transplantation, and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index(R) and Medline(R). State of Art. Over the last decade, recombinant DNA technology has allowed the large scale production of cytokines controlling the proliferation and differentiation of hemo-lymphopoietic cells. Thus, in principle, ex vivo manipulation of hemopoiesis has become feasible. The present review covers three major area of interest in experimental and clinical hematology: manipulation of hematopoietic stem/progenitor cells, cytotoxic 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 perhaps abrogating, the myelosuppression after high-dose chemotherapy. Concurrently, other important potential applications for ex vivo manipulation 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 cells capable of initiating the process of immune response. Conclusions and Perspectives. Present and future challenges in this field are represented 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 therapy programs. The selective outgrowth of normal progenitor cells over neoplastic cells to achieve tumor-free autografts may ameliorate the results of autologous transplantation. The selective production of cellular subsets to manipulate the graft versus-host and graft versus-tumor effects and anti-tumor vaccination strategies may be important to improve cellular adoptive immunotherapy.