In vivo Tissue Engineering

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.

In vivo transcription, RNA transfection, Reprogramming, Differentiation and Proteinbiosynthesis

Contact

frontend.sr-only_#{element.contextual_1.children.icon}: Prof. Dr. Meltem Avci-Adali Head of Department

frontend.sr-only_#{element.contextual_1.children.icon}: 07071 29-86605

frontend.sr-only_#{element.contextual_1.children.icon}: 07071 29-5369

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.

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.

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).

Synthetic surface - EPC mambrane specific targets initiate the binding to the capturing molecules.

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.

Selected publications:

Steinle H, Weber M, Behring A, Mau-Holzmann U, von Ohle C, Popov AF, Schlensak C, Wendel HP, Avci-Adali M. Reprogramming of urine-derived renal epithelial cells into iPSCs using srRNA and Consecutive Differentiation into Beating Cardiomyocytes. (2019) Mol Ther Nucleic Acids, 17:907-921.
Steinle H, Golombek S, Behring A, Schlensak C, Wendel HP, Avci-Adali M. Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs. (2018) Mol Ther Nucleic Acids, 13:387-398.
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, 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.