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

4 - Closed

Start Date

30 October 2008

Expected End Date

30 October 2012

Completed Date

15 November 2012

Participating Countries

Brazil
China
France
Germany
India
Indonesia
Malaysia
Netherlands
Republic of Korea

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

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

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

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

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

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

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

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

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

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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