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Arbeitsgruppe in vivo Tissue Engineering

 

Group Leader

Avci-Adali_90x90  PD Dr. Meltem Avci-Adali

  Group Leader

  Tel. 07071 29-83334

  Fax 07071 29-3617

 

 

Application of synthetic mRNA or self-replicating RNA (srRNA)

The exogenous delivery of synthetic mRNA or srRNA enables the synthesis of desired, missing, or mutated proteins in specific cells without genomic integration.

 

Meltem1_act

In our working group, these synthetic RNAs are used for: 

  • Expression of desired receptors, signaling molecules, and components of extracellular matrix (ECM)
  • The footprint-free generation of induced  pluripotent stem cells (iPSCs) from patient`s somatic cells and the following differentiation into desired cell types, such as cardiomyocytes and endothelial cells for the treatment and investigation of cardiovascular diseases.

 

Regeneration of tissues

The research group also combines biomaterials with stem cells, endothelial cells, cardiomyocytes, and biomolecules for the regeneration of tissues. Thereby, the induction of endothelialization on blood-contacting implant surfaces, hemocompatibility, and vascularization of tissues play an important role.

Biofunctionalization of blood-contacting materials for in vivo tissue engineering

EPC-Fishing2_akt_25_7_2018

 

The natural endothelium represents an ideal surface for blood contact. Thus, to create an autologous endothelium on synthetic surfaces, a bionic approach can be followed.

For this purpose, surfaces are provided with only a few nanometers thick coating of stem cell-specific capture molecules (e.g., DNA aptamers) that are able to bind the circulating endothelial progenitor cells (EPCs) directly from the blood flow to the blood-contacting surface (see Figure). 

(Link zu )
 

 

EPCs can differentiate into endothelial cells and line the synthetic surface with functional endothelium. The immobilized capture molecules mimic the natural homing factors, which allow targeted attachment of EPCs to the damaged endothelium after a vascular injury.

 

The stem cell-specific aptamers generated in the working group are primarily used for the following applications:

  • Isolation and homing of stem cells to ischemic tissues, e.g. after a heart attack.
  • In vivo colonization of implants, prostheses, or biomaterials with autologous stem cells.

To evaluate these approaches, the working group has in vitro test systems, e.g. modified Chandler loop, organotypic models, flow and rotation models for cell seeding, as well as in vivo models.

 

(Link zu )

PhD students

Heidrun Steinle

Sonia Golombek

Marbod Weber

Selected publications

M. Lescan, Perl RM, Golombek S, Pilz M, Hann L, Yasmin M, Behring A, Keller T, Nolte A, Gruhn F, Kochba E, Levin Y, Schlensak C, Wendel HP, Avci-Adali M. De novo synthesis of elastin by exogenous delivery of synthetic modified messenger RNA into skin and elastin deficient cells. (2018) Mol Ther Nucleic Acids, 11: 475-484.

 

Golombek S, Pilz M, Steinle H, Kochba E, Levin Y, Lunter D, Schlensak C, Wendel HP, Avci-Adali M. Intradermal delivery of synthetic mRNA using hollow microneedles for efficient and rapid production of exogenous proteins in skin. (2018) Mol Ther Nucleic Acids, 11:382 - 392.

 

Steinle H, Ionescu TM, Schenk S, Golombek S, Kunnakattu SJ, Özbek MT, Schlensak C, Wendel HP, Avci-Adali M. Incorporation of Synthetic mRNA in Injectable Chitosan-Alginate Hybrid Hydrogels for Local and Sustained Expression of Exogenous Proteins in Cells. (2018) Int J Mol Sci. 19(5). doi: 10.3390/ijms19051313.

 

Stoll H, Steinle H, Stang K, Kunnakattu S, Scheideler L, Neumann B, Kurz J, Degenkolbe I, Perle N, Schlensak C, Wendel HP, Avci-Adali M. Generation of large-scale DNA hydrogels with excellent blood and cell compatibility. (2017) Macromol Biosci.17(4). 

 

Guan X*, Avci-Adali M*, Alarçin E, Cheng H, Kashaf SS, Li Y, Chawla A, Jang HL, Khademhosseini A. Development of hydrogels for regenerative engineering. (2017) Biotechnol J. 12(5). 

 

Steinle H, Behring A, Schlensak C, Wendel HP, Avci-Adali M. Application of in vitro transcribed messenger RNA for cellular engineering and reprogramming: progress and challenges (2017) Stem Cells, 35(1):68-79.

 

Avci-Adali M, Behring A, Steinle H, Keller T, Krajewski S, Schlensak C, Wendel HP. In vitro synthesis of modified mRNA for induction of protein expression in human cells. (2014) JoVE. (93):e51943.

 

Avci-Adali M, Behring A, Keller T, Krajewski S, Schlensak C, Wendel HP. Optimized conditions for successful transfection of human endothelial cells with in vitro synthesized and modified mRNA for induction of protein expression. (2014) J Biol Eng. 8 (1):8

 

Avci-Adali M, Ziemer G, and Wendel HP. Induction of EPC homing on biofunctionalized vascular grafts for rapid in vivo self-endothelialization – A review of current strategies. (2010) Biotechnol. Adv. 28, 119-129

 

* contributed equally

 






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Klinisches Forschungslabor der Thorax-, Herz- und Gefäßchirurgie
Calwerstraße 7/1
72076 Tübingen
PD Dr. Meltem Avci-Adali
Tel. 07071 29-83334
Fax 07071 29-3617
E-Mail
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