Bone Marrow (Stromal) Stem Cells and Cellular Therapies

Our research

Human bone marrow (BM) contains the hematopoietic stem cells (HSC) as well as a rare population of non-hematopoietic bone marrow stromal stem cells (BMSC). The HSCs are responsible for the life-long production of the different blood cells, whereas BMSCs generate skeletal tissues and give rise to the hematopoietic microenvironment (HME).

HSC and BMSC closely interact with each other, and the HME thus plays a vital role in the regulation of hematopoiesis. On the one hand, aberrations in HSC have been demonstrated to induce changes in the HME and, on the other hand, dysfunctional BMSC have been implicated in the development and progression of hematopoietic stem cell diseases, and impaired hematopoietic recovery after hematopoietic stem cell transplantation, respectively.

One major focus of our research is therefore to study bone marrow hematopoietic and stromal stem cells and their crosstalk in healthy and diseased bone marrow, aiming to develop therapies to repair or eliminate and replace dysfunctional HSCs and BMSCs, thus leading to improved therapies for patients with hematological malignancies.

Malignant HSC can be replaced by transplantation of healthy donor stem cells (so-called hematopoietic stem cell transplantation, HSCT), which is the only curative treatment for patients with high-risk hematological malignancies. However, HSCT is a potentially dangerous procedure with severe side-effects which cause a considerable treatment-related morbidity and mortality. Therefore, another major line of research in our lab focuses on the development of novel novel and improved stem cell collection and separation technologies and transplantation biomarker assays based on acoustic sorting (acoustophoresis).

Finally, we are actively involved in the development of a GMP infrastructure that will allow to translate the therapies developed in StemTherapy and other programs into clinical advanced medicinal products (ATMP). Here, we are represented in key positions in the National Tissue Project (Vävnadsrådet) and the National Center for Advanced Medical Products, CAMP.

Aims

• Improve the treatment of patients with hematological malignancies by
• Understanding hematopoietic stroma and stroma/HSC interactions in health and disease
• Improve allogenic HSC transplantation by improved diagnostics and transplants

Impact

Despite recent progress in the diagnosis and treatment of hematopoietic cancers, too many patients succumb to their disease because of development of treatment resistance and relapse. Even the currently most effective therapy, transplantation of allogeneic hematopoietic stem cells, fails in a considerable fraction of patients and treatment-related side effects can be devastating. Our research will contribute to a better understanding of the important interplay of hematopoiesis and the stroma, thus identifying stroma aberrations that are targets for future novel stroma-directed therapies. Furthermore, our work on HSC and stroma stem cell isolation and propagation as well as the ongoing biomarker work will result in improved stem cell transplantation leading to less side effects and better survival.   

List of Team Scheding's publications

Team

(name linked to profile in Lund University research portal)

Stefan Scheding 

Principal Investigator, Stefan [dot] Scheding [at] med [dot] lu [dot] se (Stefan[dot]Scheding[at]med[dot]lu[dot]se) 

Hongzhe Li 

Researcher, Hongzhe [dot] Li [at] med [dot] lu [dot] se (Hongzhe[dot]Li[at]med[dot]lu[dot]se)

Anne Hultquist, Md, PhD

Hematopathologist, anne [dot] hultquist [at] med [dot] lu [dot] se (anne[dot]hultquist[at]med[dot]lu[dot]se)

Dang Nghiem Vo

Postdoc, Dang [dot] Nghiem_Vo [at] med [dot] lu [dot] se (Dang[dot]Nghiem_Vo[at]med[dot]lu[dot]se)

Marie Magnusson 

Laboratory technician, Marie [dot] Magnusson [at] med [dot] lu [dot] se (Marie[dot]Magnusson[at]med[dot]lu[dot]se) 

Alba Lillo

Student

Luca Spiessens

Student