Cytotherapy, 2015; 17: 693e694
INTRODUCTION
Umbilical cord blood: advances and opportunities NINA SHAH1 & JAAP JAN BOELENS2,3 1
Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, Texas, USA; 2Department of Pediatrics, Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht; and 3Laboratory for Translational Immunology, Tumor-Immunology Section, University Medical Center Utrecht, Utrecht, the Netherlands
Since the first umbilical cord blood (CB) transplant for hematopoietic reconstitution in 1988, more than 30,000 CB transplants have been performed. CB transplants are now established as a viable hematopoietic stem cell source worldwide. The resulting experience has not only developed our knowledge of CB transplant but has also opened a new area of research in which CB is used as an active therapy for disease. In this issue of Cytotherapy, we focus on the many advances and potential applications for CB. Our journey takes us from our solid but still-evolving knowledge of hematopoietic stem cell transplant to developing experience with immunotherapy and finally to the still-primordial experience with cord blood/tissue-derived mesenchymal stromal cells, inducible pluripotent stem cells and therapies beyond cancer, including regenerative medicine. In the first section of this issue, we examine our cumulative experience with CB transplantation. Milano and Boelens discuss comparisons with other stem cell sources, and Spierings and Thus explain how our deeper understanding of antigens and genetics can help us to better optimize CB unit selection. We then revisit the longstanding challenge of CB transplantation: cell dose—but with a refreshed perspective in light of multiple recently published options for increasing CD34þ dose. Our second section focuses on CB immunotherapy. In a series of reviews, we shed light on this novel and exciting role for CB. Hanley and Brunstein illustrate how the CB unit can be used to diversify
into multiple supportive immunotherapy products, including virus-specific T cells and regulatory T cells. Cany et al. go further in this new landscape of opportunities to discuss the potential anti-tumor cellular therapies that can be derived from a single CB unit. These articles broaden our perspective on CB to include a therapeutic potential over and above a merely reconstructive one. In the final section of this issue, we call on experts to describe the very early experience with CB for applications beyond immunology and treatment of malignancy. In retrospect, it should have been obvious that CB could yield alternative, nonhematopoietic stem cell products, but, only in recent years has this been rigorously studied. The promise of these incredibly exciting applications has renewed interest in CB as a therapy worthy of further development. More importantly, it provides a ray of hope for patients with rare and irreversible diseases. To this end, several national organizations and private companies have been developing CB therapeutics for use in the malignant and the benign settings. This area is unchartered territory for investigators and investors and requires a solid partnership between academia and industry. Many factors in CB therapy are unknown—most notably, cost. As discussed by several authors in this issue, the cost of pre-clinical development and eventual Good Manufacturing Practicee compliant translation initially may seem overwhelming but can only be reduced by diligence and repeated experience with these products. Although science and finance must synergize to develop CB transplant and therapies, they must
Correspondence: Nina Shah, MD, Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423 Houston, TX 77030. E-mail: [email protected] (Received 2 March 2015; accepted 2 March 2015) ISSN 1465-3249 Copyright Ó 2015, International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcyt.2015.03.001
694
N. Shah & J. J. Boelens
work within the structure of regulatory oversight. Currently, this is an individualized process that varies for each developed product. However, as was the case with pharmaceuticals and now with immunotherapies, the accumulation of data and experiences will also streamline the process to bring it to reality. As a voice for the International Society of Cell Therapy (ISCT), the mission of Cytotherapy is to be a
resource for discussions on innovations in stem cell transplantation, immunotherapy and regenerative medicine. To this end, it is fitting that an issue of this journal is devoted to CB, which plays an important role in all three areas. We are delighted to provide this presentation on the achievements in the field of CB. We are even more thrilled to provide an exciting glimpse of the future of this naturally occurring and most plentiful human resource.
INTRODUCTION
Umbilical cord blood: advances and opportunities NINA SHAH1 & JAAP JAN BOELENS2,3 1
Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, Texas, USA; 2Department of Pediatrics, Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht; and 3Laboratory for Translational Immunology, Tumor-Immunology Section, University Medical Center Utrecht, Utrecht, the Netherlands
Since the first umbilical cord blood (CB) transplant for hematopoietic reconstitution in 1988, more than 30,000 CB transplants have been performed. CB transplants are now established as a viable hematopoietic stem cell source worldwide. The resulting experience has not only developed our knowledge of CB transplant but has also opened a new area of research in which CB is used as an active therapy for disease. In this issue of Cytotherapy, we focus on the many advances and potential applications for CB. Our journey takes us from our solid but still-evolving knowledge of hematopoietic stem cell transplant to developing experience with immunotherapy and finally to the still-primordial experience with cord blood/tissue-derived mesenchymal stromal cells, inducible pluripotent stem cells and therapies beyond cancer, including regenerative medicine. In the first section of this issue, we examine our cumulative experience with CB transplantation. Milano and Boelens discuss comparisons with other stem cell sources, and Spierings and Thus explain how our deeper understanding of antigens and genetics can help us to better optimize CB unit selection. We then revisit the longstanding challenge of CB transplantation: cell dose—but with a refreshed perspective in light of multiple recently published options for increasing CD34þ dose. Our second section focuses on CB immunotherapy. In a series of reviews, we shed light on this novel and exciting role for CB. Hanley and Brunstein illustrate how the CB unit can be used to diversify
into multiple supportive immunotherapy products, including virus-specific T cells and regulatory T cells. Cany et al. go further in this new landscape of opportunities to discuss the potential anti-tumor cellular therapies that can be derived from a single CB unit. These articles broaden our perspective on CB to include a therapeutic potential over and above a merely reconstructive one. In the final section of this issue, we call on experts to describe the very early experience with CB for applications beyond immunology and treatment of malignancy. In retrospect, it should have been obvious that CB could yield alternative, nonhematopoietic stem cell products, but, only in recent years has this been rigorously studied. The promise of these incredibly exciting applications has renewed interest in CB as a therapy worthy of further development. More importantly, it provides a ray of hope for patients with rare and irreversible diseases. To this end, several national organizations and private companies have been developing CB therapeutics for use in the malignant and the benign settings. This area is unchartered territory for investigators and investors and requires a solid partnership between academia and industry. Many factors in CB therapy are unknown—most notably, cost. As discussed by several authors in this issue, the cost of pre-clinical development and eventual Good Manufacturing Practicee compliant translation initially may seem overwhelming but can only be reduced by diligence and repeated experience with these products. Although science and finance must synergize to develop CB transplant and therapies, they must
Correspondence: Nina Shah, MD, Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423 Houston, TX 77030. E-mail: [email protected] (Received 2 March 2015; accepted 2 March 2015) ISSN 1465-3249 Copyright Ó 2015, International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcyt.2015.03.001
694
N. Shah & J. J. Boelens
work within the structure of regulatory oversight. Currently, this is an individualized process that varies for each developed product. However, as was the case with pharmaceuticals and now with immunotherapies, the accumulation of data and experiences will also streamline the process to bring it to reality. As a voice for the International Society of Cell Therapy (ISCT), the mission of Cytotherapy is to be a
resource for discussions on innovations in stem cell transplantation, immunotherapy and regenerative medicine. To this end, it is fitting that an issue of this journal is devoted to CB, which plays an important role in all three areas. We are delighted to provide this presentation on the achievements in the field of CB. We are even more thrilled to provide an exciting glimpse of the future of this naturally occurring and most plentiful human resource.
