Projects / Programmes
Application of human stem cells for therapy
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B500 |
Biomedical sciences |
Immunology, serology, transplantation |
| B490 |
Biomedical sciences |
Haematology, extracellular fluids |
- stem cell, embryonic stem cell, haematopoietic stem cell
Researchers (22)
Organisations (2)
Abstract
Therapy with stem cells represents a logical continuation of current blood transfusion therapy, which will be supplemented by cellular therapies in future. Research of various types of stem cells in the bone marrow; i.e. cell types that have been reported to coexist in the bone marrow of the adult, i.e. haematopoietic stem cell, the mesenchymal stem cell, haemangioblast, and the multipotent adult progenitor cells (MAPC), which can all be differentiated into practically any type of the ecto-, endo- and mesodermal cell lines. Since the current methods of isolation and characterisation are not adequate, expensive and time consuming, better source of stem cells are looked for. One option is to use embrional-like stem cell line isolated from the cord blood, which can be differentiated into various cell types. It is not yet clear, whether they can be differentiated into the haemopoietic progenitors and/or myeloid and lymphatic lines. The purpose of the investigation is therefore to find out whether this cell lines can be differentiated and multiplied into the megakaryoblast and erythroblast cell lines. In this way we shall try to investigate whether this method of blood cell cultivation is an viable alternative to the current ways of blood components procurement.
Significance for science
Cell therapies, differentiation studies and SC research are one of basic research/developmental directions in the biomedicine in last decade. Potential of different SCs is enormous and it gives, along with the use of new post-genomic technologies and system biology, answers to some key questions in biomedicine, such as treatment of cancer, genetic diseases, etc. The central issues consider the use of ESCs, which is highly ethically questionable. Therefore alternative approaches are essential, using the embryonic-like SCs from partal tissues such as umbilical cord blood (UCB). A successful development of these cells will enable understanding and control of SC development, which will substitute the use of ESCs. This would represent a major scientific improvement in a global aspect.
The central problems of isolation and characterisation of primitive SCs from UCB and further differentiation into nerve cells was documented by our group in the article in Nature protocols
(McGuckin et al. Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nat Protoc 2008; 3(6): 1046-1055). These cells we further developed into the endodermis line (liver and beta-cells of pancreas), as documented in doctoral thesis of Strbad M. (in preparation). During this work some unexpected discoveries appeared in our group, such as the existence of similar SCs in adult human ovary (see Virant-Klun in sod. Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes. Differentiation (Lond.), 2008. Oct;76(8):843-56). These ESC-A like cells were later developed in vitro into parthenogenetic like blastocysts, confirming that the cells in question are highly pluripotent (see Virant-Klun in sod. Parthenogenetic embryo-like structures in the human ovarian surface epithelium cell culture in postmenopausal women with no naturally present follicles and oocytes. Stem cells dev., 2009, vol. 18, no. 1, str. 137-149). We have checked if similar SCs existed in adult bone marrow, which was positively confirmed by a BSc research work (Jež, Mojca. Identifikacija celic z embrionalnimi lastnostmi v kostnem mozgu odraslega človeka : diplomsko delo, Univerza v Ljubljani, 2008). In parallel, SCs were isolated from the adipose tissues and they were shown to be useful for regeneration of bones (see Fröhlich Mirjam et al. Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue eng. part A, 2010, letn. 16, št. 1, str. 179-189).
Our research has shown that relevant scientific questions were addressed and majority of technical questions were solved. The cultivation, isolation and characterisation techniques for UCB SCs cultivation were mastered and the results were relevantly conveyed into the international scientific community. Our result will contribute to further discoveries and improvements in the SC isolation from the bone marrow and blood, expansion of methodologies for the characterisation of SCs and their progenitors, development of protocols for differentiation into blood cells as well as provision of techniques for the acquiring and purifying various SCs for clinical use.
Significance for the country
Good results of our project enabled the possibility of clinical use of SC lines, improvement of SC isolation from the bone marrow and peripheral blood, broadening of methodologies and instruments for characterization of SCs and progenitor cells, further development of directed differentiation of hSC and mastering technologies for the isolation and purification of different SCs. Our results will serve to the development of transfusion medicine and in long term, to other clinical medicine oriented research groups, which will need these methodologies for therapeutic purposes of certain disease. In our case, we demonstrated a conversion of UCB SCs into pancreatic beta cells and development into blood cells. Our target user groups are clinical wards for haematology and bone marrow transplantation, surgery of liver and pancreas, cardiology, urology, plastic surgery, trauma, orthopedics, and dental surgery. On the other hand, results could be used in SMEs and pharmaceutical industry.
This work will contribute the top medical services that will enable treatments and consequent high level of health. Supplementing the diseased tissues is already contributing to the current treatment and rehabilitation. In last 10 years we have succeeded to form a solid infrastructure, personnel and achievements on the field of medical biotech. Our systematic work has already helped to several hundred previously non-healable patients. Cellular therapies in Slovenia could become a representative activity . This medical field is also a propulsive industry, that is ecology-friendly, enabling further development of economy, including medicine, health tourism, educational system, and finally, scientific development of our society.
Most important scientific results
Annual report
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
