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Development of 3D culture models for human ucmMSC-derived hepatocytes for predictive toxicology and cell therapy

iMed.ULisboa/ FFULisboa Research Institute for Medicines/ Faculdade de Farmácia, Universidade de Lisboa
Project classification

Scientific area

3.1 Basic medicine

Discipline(s)

Toxicology
Pharmacology and pharmacy
Human genetics
Anatomy and morphology (plant science go to scientific area 1.6)
Physiology (including cytology)

Project description

Project title

Development of 3D culture models for human ucmMSC-derived hepatocytes for predictive toxicology and cell therapy

Scientific Coordinator's name:

Joana Miranda

Scientific Coordinator's e-mail:

jmiranda@ff.ul.pt

Principal R&D Unit:

iMed.UL/FFUL

Other R&D Units involved in the project:

ECBIO, Investigação e Desenvolvimento em Biotecnologia, S.A. (ECBIO); Charité - Universitätsmedizin Berlin (Charité)

Project keyword(s)

ucmMSCs; hepatocyte-like cells; three-dimensional cultures (3D); cell therapy; in vitro toxicology

Short abstract and comments

The ever-lasting search for the golden standard in vitro hepatocyte model for toxicological drug screening still continues. The major issues with currently available models are low biotransformation activity together with short periods of time and species origin. Differentiation of stem cells (SC) into hepatocyte-like cells (HLCs) has been suggested, however, a completely mature HLC population derived from SC has not yet been achieved. Moving towards a better system than the existing ones, I aim to develop a novel in vitro model of HLC differentiated from human umbilical cord tissue-derived stem cells with mesenchymal properties (UCXR cells) under three-dimensional (3D) culture conditions. Such cultures conditions will create a scalable and more relevant environment for the differentiation process, closer to the in vivo. Thus, a representative, thorough and standardized model will be developed to early evaluate drug safety, meeting pharmaceutical industry needs and taking a step forward in predictive toxicology.

Potential uses/indications

The project aims to address and solve the following problems: a) The difficult task of obtaining (and maintaining) functional hepatocytes in vitro in quality and numbers that would be compatible to wide scope drug screening – important for the pharmaceutical industry. b) The development of a 3D culture system for ucmMSC culture and expansion would be important to obtain cell numbers compatible to most cell therapy protocols. The expansion factor that could hopefully be obtained with such a system would be a major breakthrough for ucmMSC allogenic applications, limited by the cells availability.

Status

Ongoing

Partner Status: Seeking Partners?

No

Grant number (QREN, FP7, Eureka, etc)

PTDC/SAU-TOX/110457/2009

Last edited on

2013-11-04 13:27:48

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