Haematopoietic Stem Cells (HSCs) : Haematopoietic Stem Cells (HSCs) Gary Morris, Nathalie Saurat, Julian Peat, Angela Hsu
Background : Background Multi-potent Stem Cells
Differentiate into all types of blood cell
Constitute 1/10000 cells of myeloid tissue
Myeloid tissue: Mainly found in bone marrow, but also liver and spleen
Self renewal
maintain a basal level in their niche environment
Differentiation : Differentiation
Isolation : Isolation Direct removal from hip using needle and syringe
Pre-treating blood with cytokines to induce cells to be released from bone marrow, allowing collection from blood
Umbilical cord and placenta blood for clinical use
Fetal spleen, fetal liver
Bone Marrow : Bone Marrow
Niche : Niche Stem cells reside in specialized microenvironments created by supporting cells
Stem cell self renewal occurs in the stem cell niche in the bone marrow
Key signals present in this niche are important in self renewal
Niche : Niche Niche contains reticular cells that secrete a chemokine promoting HSC maintenance Sugiyama et al. (2006). Occurs in spleen and liver as well as bone marrow.
Osteoblasts and osteoclasts secrete or activate a variety of factors that regulate HSC function and number
Understanding stem cell niche will help generate larger populations of HSCs ex vivo that can be used therapeutically
Maintaining HSCs in niche : Maintaining HSCs in niche
Markers : Markers Help to localise HSCs
Clinical Applications : Clinical Applications HSC rescue in cancer chemotherapy
Marrow Donation
Attack untreatable tumors
Leukemia and Lymphoma
Inherited blood disorders
Sickle cell anemia
Immunodeficiency syndromes
Diabetes, rheumatoid arthritis, system lupus erythematosis
Future Directions : Future Directions Treat infectious diseases of the blood with autologous gene modified HSCs to produce cells that resist infection
AIDs, TB, malaria, leprosy
Engineering of stem cells to be free of the HLA markers so that immunorejection is no longer a problem.
Determining the optimal timing for foetal transplantation (discrete window for transplantation)
Finding ways to minimise graft vs. host disease and maximise graft vs tumour effects
Pros and Cons in Brief : Pros and Cons in Brief Cons
Conditioning for transplantation is associated with morbidity
graft-verus-host disease (GVHD)
Related problem of impaired immune reconstitution
Difficult to get enough HSCs to treat adults Pros
Can substitute for the defective hematopoietic organ
Can confer of antitumor effects (graft-versus-tumor [GVT])
Can induce immune tolerance
One of the most accessible adult stem cell types
Challenges : Challenges Functional and phenotypic heterogeneity of HSCs
Getting enough HSCs to treat an adult is difficult due to:
The low numbers of HSCs that can be accessed
The lack of methods for their long-term propagation in vitro
Further research is needed into:
Ways to expand subpopulations of cell types in culture
Ways to mix stem cells from multiple donors