Stemcel biology / Regenerative medicine (incl. blood transfusion)

The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Immunohematology and Blood Transfusion.

Aim and focus

The research in the cluster of regenerative medicine focuses on stem cell biology, stem cell therapy, blood transfusion medicine and immune monitoring.. The focus on stem cells comprises both hematopoietic and non-hematopoietic stem cells, especially mesenchymal stem cells. The hematopoietic stem cell program aims at understanding several key processes crucial for stem cell biology, namely: the regulation of self-renewal, multi-lineage differentiation, mobilization and signal transduction. Interaction with the hematopoietic microenvironment (stem cell niche, stromal cells) is closely associated to these processes. One of the major aims is to develop effective stem cell expansion programs applicable in clinical protocols. This also forms the basis for the development of a hematopoietic stem cell-based gene therapy program. The non-hematopoietic stem cell research focuses mainly on the clinical application of mesenchymal stem cells, insulin-producing stem cells (islet transplantation) and the use of tissue-specific stem cells for tissue repair. Within the department an extensive translational and clinical application program has been developed that includes transplantation of hematopoietic stem cells, mesenchymal stem cells and islets from pancreas. Potential novel cell therapies have been developed in the area of dendritic cell therapy and NK cell therapy. Areas of application include haematological malignancies and immunodeficiencies, autoimmune disorders (Crohn’s disease, type 1 diabetes), organ transplantation and tissue regeneration (cardiac repair, lung repair). These programs are closely linked to the blood transfusion service that also focuses on epidemiological studies. The research in the area of classical Blood transfusions is closely aligned to two of the main medical needs of the national blood supply organization Sanquin namely: Anaemia and Haemostasis. The mainly clinical trial oriented research on these themes is organized and executed by the LUMC-Sanquin Jon J van Rood Centre for Clinical Transfusion Research (CCTR), and supervised by professor de Haas and Zwaginga (IHB-Sanquin) and van der Bom (Clinical epidemiology-Sanquin). Immune monitoring is a rapidly advancing area that utilizes expertise in the field of immunology combined with cutting edge technology (particularly flow cytometry) to study the immune system in health and disease. Multiparametric analysis of the many different (sub)populations of immune cells is highly relevant for understanding the development of the immune system and for monitoring of immune responses induced by infection, vaccination, or cell and tissue transplantation. A major aim is to develop and validate an immune monitoring program for diagnosis, prognosis and monitoring of therapies for a range of diseases, including immunodeficiencies, auto-immune diseases, leukemias & lymphomas, and solid tumors

Position in international context

The research in regenerative medicine within the department of Immunohematology and Blood Transfusion (IHB) is imbedded in the theme group “Regenerative Medicine” of the LUMC. In this group, substantial critical mass has been obtained over the past years by the recruitment of professor Christine Mummery (MCB, developmental biology) and professor Frank Staal (IHB, molecular stem cell biology) and professor Jacques J.M. van Dongen (IHB, Immune Monitoring). Thanks to the integration of all research activities in this theme group, several large scale collaborative grants have been obtained, funded by national as well as international programs. Strong international collaborations exist with centers in Europe and the US. This relates not only to research but also the clinical application of stem cell therapy. The department has played a leading role in establishing an international expansion consortium for mesenchymal stromal cells and is currently conducting a randomized phase III study with MSC in steroid refractory acute GvHD. To this end, the availability of a large and fully-accredited GMP facility is a major advantage. Within the LUMC, numerous collaborations have been established with clinical departments. The Clinical Blood transfusion research the last 5 years has led to key publications in the field among which on RBC allo-immunization risk factors, unique (in size and epidemiological methodology) both RCT and case control clinical trials in again the area of RBC and blood platelet- allo-immunization, bleeding risk factors and functionality of pathogen reduced blood platelets. The LUMC in this regards has extended its role as ‘the national centre for clinical transfusion medicine’.

Content / highlights / achievements

  • Through multiple national and EU-grants, the Mesenchymal Stromal Cell therapy program focuses on showing that MSC’s may be able to modulate in-vivo immune responses in the setting of allogeneic stem cell transplantation, organ transplantation and or autoimmune disorders. 
  • This notion is currently further studied in (randomized) clinical trials. Patient referrals are coming from other academic centers in the Netherlands in Europe. 
  • The gene therapy program is close to translation to clinical application in the area of immune deficiencies in children. Recently a large EU H2020 grant on RAG1 SCID Severe Combined Immune Deficiency) has been awarded, coordinated by Prof Staal. Thus, translational aspects are an integral part of the research activities in the departments involved 
  • The department has been assigned the official center for clinical transfusion epidemiological studies by the National Blood Bank Sanquin Foundation and has a clear and national role in cell therapy and clinical blood transfusion related epidemiology. In this context a number of clinical trials is ongoing, relating to pathogen reduction, cost effectiveness and allo-immunization. 
  • In 2016 Prof JJM van Dongen (from Erasmus MC in Rotterdam) joined the department as professor in Medical Immunology. Within the IMI-PERISCOPE project, his team is developing a platform for monitoring the immune response to Bordetella pertussis infection and vaccination. The ERC Advanced TiMaScan project develops and applies additional advanced immune monitoring strategies, particularly flow cytometric scanning of circulating tissue macrophages, to detect cancer-specific protein fragments and relate their presence to disease status, providing a new tool for early diagnosis and treatment monitoring of cancer.
  • In addition to his own research programs, the main task of Professor Van Dongen is to establish a harmonized Platform for Immune Monitoring, accessible for al clinical departments in LUMC.
  • Per January 2017 the Flow cytometry Core Facility (FCF) has been established, which serves all flow cytometry users in LUMC. Prof. dr. F.J.T. Staal and Prof. dr. J.J.M. van Dongen are supervising and coordinating the FCF.
  • In 2016, Prof Roep continued his career in California. He will however remain active in diabetes research in LUMC and will continue his research group in Leiden.

Future themes

Within the research cluster Regenerative Medicine, we will strengthen the research at the transition of stem cell biology and immunology. In particular, this will focus on combination of regenerative therapies for a variety of disorders, in combination with basic studies aimed at unravelling immune mechanisms underlying allo- and autoimmunity. The department will expand the gene therapy program and will consider setting up a vector facility, in collaboration with the Medizinische Hochschule in Hannover (MHH). Finally, in close collaboration with Sanquin Foundation, we will further strengthen the clinical transfusion research program. The immune monitoring platform will be applied in these and other programs for basic, translational and clinical research, as well as in new clinical diagnostics.

Cohesion within LUMC

The RM group within the IHB maintains very strong interactions with a large number of clinical departments with whom we collaborate in the translational studies testing gene and cell therapy products in clinical trials. The gene therapy pre-clinical work, vector and viral batch design is done in collaboration with molecular cell biology, while the more fundamental work on MSC product variability is done in collaboration with the centre for proteomics and metabolomics.
The vast portfolio of gene therapy activities within the LUMC  ranging from fundamental vector design to clinical application has thus far been rather invisible to the outside world. Hence on the initiatives of Staal (IHB), van derMaarel (hum Gen) and Hoeben (MCB) the Leiden Gene Therapy Platform (LGTP) has been established. Its goal is better collaboration, visibility within and outside the LUMC, coordinating Medical Delta activities in the realm of gene therapy and joint funding applications.
The supportive Transfusion medicine unit is a multidisciplinary unit with close collaborations with close collaborations established with a variety of clinical departments. Furthermore, the monitoring of the immunomodulatory effects of allo- and auto immune responses fits well in the immunomonitoring platform within the department.