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          Improving Outcomes in Radiotherapy using Novel Biotechnologies: Modification of Tissue Reactions and the Use of Stem Cell Therapeutics

          Closed for proposals

          Project Type

          Coordinated Research Project

          Project Code

          E33032

          CRP

          1634

          Approved Date

          9 September 2008

          Status

          Closed

          Start Date

          30 October 2008

          Expected End Date

          30 October 2012

          Completed Date

          15 November 2012

          Description

          During radiotherapy, the most important dose-limiting factor is sensitivity of the normal tissue lying in the radiation field. This can result in organ damage or severe normal tissue reactions. Radiation-induced organ damage is mainly caused by stem cell sterilization and hence leading to a reduced reconstitution of functional cells in the irradiated organ. Replenishment of the depleted stem cell compartment should allow regeneration of irradiated tissues/organs. The major aim of the project is to facilitate and disseminate stem cell research in IAEA Member States to prevent radiation-induced damage to normal tissues/organs. If this approach has proven to be successful in pre-clinical studies, stem cell therapy could be tested in future clinical trials. Moreover, this newly acquired knowledge/expertise could also be used to design new strategies in the treatment of victims of radiation accidents

          Objectives

          The major aim of the project was to provide Member States with new and relevant knowledge on stem cell therapeutics (i.e. optimization of techniques) to prevent radiation-induced damage to normal organs/normal tissues. If this approach has proven to be successful in pre-clinical studies, stem cell therapy could be tested in future clinical trials. Moreover, newly acquired knowledge/expertise could also be used to initiate new strategies in the treatment of victims of radiation accidents. The initiation of collaboration between relevant laboratories; establishing of exchange programs and joint applications for additional funding will be stimulated.

          Specific objectives

          ? Which cells/compounds or combinations have the highest potential of reducing radiation- induced tissue toxicity in a specific tissue?
          ? What are the risks of stem cell therapy; i.e. does stem cell therapy later induce cancer, teratoma’s or malformations?

          In order to develop experimental protocols for the amelioration of radiotherapy-induced side effects by stem cell therapy a number of specific research questions need to be answered:
          ? What is (are) the optimal time-point(s) for stem cell therapy; one ore more treatments and when?
          ? What is the optimal number of stem cells to be transplanted; or optimal drug dose ("cocktail" of growth factors); optimum exposure to molecular/viral vectors
          ? What is the best routing; local administration of the cells/compound/drug or systemic administration (i.e. via IV injections)?

          To successfully use stem cell therapy it is important to understand:
          ? The nature and qualities of different types of stem cells,
          ? The mechanism by which stem cells differentiate into mature, functional cells and,
          ? Their capacity to repair damaged (irradiated) tissues/organs in a variety of experimental animal models.

          Impact

          Participating institutes have exchanged relevant protocols and several initiatives for future collaboration have been established. Research agreement holders are frequently consulted by the other participating institutes regarding protocols, methodology, training, fellowships etc.

          Relevance

          The CRP is very relevant to the Agency's Project and to Member States.

          CRP Publications

          Type

          Journal Article

          Year

          2011

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/21719134

          Description

          Nanduri, L. S., M. Maimets, et al. (2011). "Regeneration of irradiated salivary glands with stem cell marker expressing cells." Radiother Oncol 99(3): 367-372.

          Country/Organization

          The Netherlands / University of Groningen

          Type

          Journal Article

          Year

          2012

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/22253725

          Description

          Tiwari, S., M. J. Ali, et al. (2012). "Establishing human lacrimal gland cultures with secretory function." PLoS One 7(1): e29458.

          Country/Organization

          India / L. V. Prasad Eye Institute

          Type

          Journal Article

          Year

          2010

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/20970030

          Description

          Vissink, A., J. B. Mitchell, et al. (2010). "Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers." Int J Radiat Oncol Biol Phys 78(4): 983-991.

          Country/Organization

          The Netherlands / University of Groningen

          Type

          Journal Article

          Year

          2009

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/19625095

          Description

          Feng, J., M. van der Zwaag, et al. (2009). "Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation." Radiother Oncol 92(3): 466-471.

          Country/Organization

          The Netherlands / University of Groningen

          Type

          Journal Article

          Year

          2011

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/20796229

          Description

          Coppes, R. P. and M. A. Stokman (2011). "Stem cells and the repair of radiation-induced salivary gland damage." Oral Dis 17(2): 143-153.

          Country/Organization

          The Netherlands / University of Groningen

          Type

          Journal Article

          Year

          2010

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/20583978

          Description

          Monceau, V., N. Pasinetti, et al. (2010). "Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity." Curr Drug Targets 11(11): 1395-1404.

          Country/Organization

          France / Institut de Radioprotection et de Surete Nucleaire/Institut Gustave Roussy

          Type

          Journal Article

          Year

          2011

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/21666950

          Description

          Alfaqeh, H. H., C. K. Hui, et al. (2011). "Growth medium with low serum and transforming growth factor beta 3 promotes better chondrogenesis of bone marrow-derived stem cells in vitro and in vivo." Saudi Med J 32(6): 640-641.

          Country/Organization

          Malaysia / Universiti Kebangsaan Malaysia Medical Centre

          Type

          Journal Article

          Year

          2012

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/22358233

          Description

          Hamid, A. A., R. B. Idrus, et al. (2012). "Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation." Clinics (Sao Paulo) 67(2): 99-106.

          Country/Organization

          Malaysia / Universiti Kebangsaan Malaysia Medical Centre

          Type

          Journal Article

          Year

          2011

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/20976667

          Description

          Saad, A. Z., A. S. Halim, et al. (2011). "The use of glycerol-preserved skin allograft in conjunction with reconstructive and flap surgery: seven years of experience." J Reconstr Microsurg 27(2): 103-108.

          Country/Organization

          Malaysia / Hospital Universiti Sains Malaysia

          Type

          Journal Article

          Year

          2013

          Publication URL

          http://www.ncbi.nlm.nih.gov/pubmed/23335219

          Description

          Pringle, S., R. van Os, et al. (2013). "Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia." Stem Cells.

          Country/Organization

          The Netherlands / University of Groningen

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