LSFM4LIFE Progress

Reporting Period 1

The first phase of the project ran from January 2016 to June 2017.


Context and objectives


The cellular therapy with beta-cells obtained by differentiating adult stem cells can realize the dream of a curative therapy of T1D. The stem cell approach aims to establish a virtually endless source of beta-cells, cultured according to the highest safety standards defined by EMA (European Medicine Agency) and FDA (Federal Drug Administration). Moreover, stem cell-derived beta-cells are suitable for autologous transplantation, which avoids immunosuppressive treatment.

A fundamental issue concerns the type of stem cells of choice. While embryonic stem cells (ESCs) pose significant ethical challenges, inducible pluripotent stem cells (iPSCs) could have a safety issue due to the activation of oncogenes during the reprogramming of somatic cells.

A novel strategy that consists in the isolation and culture of pancreas progenitor cells (human pancreas organoids, hPOs) allows overcoming the drawbacks of both ESCs and iPSCs.

The main goal of LSFM4LIFE is to achieve the culture and differentiation of therapeutic batches of hPOs accordingly to Good Manufacturing Practice (GMP) quality control criteria, qualifying them for clinical testing in patients.

Work performed so far


Meritxell Huch’s and Kourosh Saeb-Parsy’s labs in Cambridge established 25 lines of hPOs from healthy donors, with a success rate of 81%. These were then made available to the other project partners for performing the different tasks.

Meritxell Huch’s group improved the formulation of the media for the culture of pancreas organoids in vitro. Moreover, their long-term genetic stability and safety in vivo was analyzed by Kourosh Saeb-Parsy’s group by transplanting the organoids under the kidney capsule of immunodeficient mice.

The close collaboration between the groups in Cambridge, Frankfurt and Switzerland (InSphero) produced robust assays to test the proliferation and differentiation of the pancreas organoids, establishing an initial panel of quality assurance criteria.

Moreover, the group at the University of Frankfurt developed novel optical technology for the imaging of organoids in three-dimension with Light Sheet Fluorescence Microscopy (LSFM), as well as a novel laboratory tool for the recovery of organoids from the culture wells. Two patents concerning these innovations were submitted.

A remarkable amount of work was performed by Cellendes (Reutlingen), which successfully generated a biomimetic synthetic hydrogel that supports the growth of the organoids. Therefore, the goal of exchanging Matrigel (which is a hydrogel of animal origin unsuitable for clinical application) with a GMP-level hydrogel that is completely safe for human and 3R-compatible is getting closer.

LSFM4LIFE’s GMP experts at the Cell Factory in Milan and Lonza Netherlands made great progress for converting the laboratory-scale culture of the organoids to a GMP-level process, pursuing the final goal of translating hPO culture into a commercial Advanced Therapeutic Medicinal Product (ATMP).

The LSFM4LIFE consortium is also strongly committed to informing T1D patients and their families, as well as medical doctors, about the ongoing research and the therapeutic potential of hPOs. Several presentations to patients and medical doctors have been given by LSFM4LIFE’s scientific coordinator Francesco Pampaloni.

Progress and impact


hPOs produced at GMP-level as a long-term source of pancreas stem cells represent a breakthrough in the cellular therapy of T1D. A further groundbreaking and ambitious goal is the production of a cost-effective surrogate for Matrigel.

LSFM4LIFE also advances the field of cell-based assay by developing standardized assays on pancreas organoids in a multi-well format for drug and toxicity screening.

Moreover, with the high-throughput light sheet microscope (HT-LSFM) LSFM4LIFE realizes an innovative optical technology for the imaging of 3D tissues, which shows much better performance than state-of-the-art confocal fluorescence microscopes in terms of speed, resolution and photo-bleaching.

Reporting Period 2

The second phase of the project ran from July 2017 to December 2018. We will post our results here soon.


Reporting Period 3

The last phase of the project runs from January 2019 to December 2019.