Leukemias are blood cancers that produce abnormal cells that disrupt the vital functions of our blood system. The mechanisms involved in this deregulation are difficult to study, as these cells reside in the bone marrow, where microscopes have no access. The CytoMorpho Lab team (CEA-Irig) has found a way around this problem, and has succeeded in observing these tumor cells in action.
Using microfluidic chips, the team was able to recreate an “artificial niche”, which reproduces in a minimalist, structured way the environment in which stem cells, whether healthy or tumoral, are found in bone marrow. In these chips, with their regular geometry, where the number and position of stem cells can be controlled, and whose transparency gives free access to the best microscopes, the team was able to observe the shape and even the inner architecture of leukemia cells.
Within a cell, everything is very well organized. Space is compartmentalized, and proteins are transported along a well-defined axis. The orientation of intracellular transport constitutes the cell's polarity axis. It determines how cells communicate with neighboring cells. It was the orientation of this polarity axis that CytoMorpho Lab researchers were able to measure in healthy stem cells and tumor cells.
These cells, from patients undergoing leukemia treatment at the Hôpital Saint Louis, were recovered and inserted into artificial niches previously loaded with stromal cells to mimic their natural environment in the bone marrow.
By this way, it was discovered that blood stem cells taken from healthy patients oriented their polarity towards their point of contact with stromal cells, whereas those taken from leukemia patients were randomly oriented.
In addition to highlight new insights of research into the causes and progression of leukemia, the transparent microfluidic device used in this work could enable the development of new diagnostic tests based on observation of the morphology and behavior of patient cells. In addition, the ability of these chips to host primary human cells to mimic physiological conditions close to those of the patient, could also be used for new therapeutic strategies.
Financements:
Les travaux dirigés par Manuel Théry ont été financés par l'Agence Nationale pour la Recherche (AAPG2022-PRC-SHARP et ANR-23-CHBS-0013), la fondation Bettencourt-Schueller, la fondation Schlumberger pour l'éducation et la recherche (en soutien aux travaux de M.T.), le centre national de médecine de précision sur les leucémies (THEMA) de l'Institut de Recherche Saint Louis et la société Bristol Myers Squibb. Les travaux dirigés par Lina Benajiba ont été financés par, l'Institut National du Cancer (PRTK 2022-192), la Ligue Nationale Contre le Cancer, le programme ATIP-Avenir de la fondation Bettencourt-Schueller, le Site de Recherche Intégrée sur le Cancer “InsiTu" et l'Institut de la Leucémie Paris Saint Louis.
Collaboration : Lina Benajiba, INSERM U944 & INSERM 1427, Institut de Recherche Saint Louis (IRSL), Centre d'Investigation Clinique, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.
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Fundings:
The work directed by Manuel Théry was funded by the French National Research Agency (AAPG2022-PRC-SHARP and ANR-23-CHBS-0013), the Bettencourt-Schueller Foundation, the Schlumberger Foundation for Education and Research (in support of M.T.'s work), the National Center for Precision Medicine in Leukemia (THEMA) at the Saint Louis Research Institute and Bristol Myers Squibb. The work led by Lina Benajiba was funded by the Institut National du Cancer (PRTK 2022-192), the Ligue Nationale Contre le Cancer, the ATIP-Avenir program of the Bettencourt-Schueller Foundation, the “InsiTu” Integrated Cancer Research Site and the Institut de la Leucémie Paris Saint Louis.
Collaboration :
Lina Benajiba, INSERM U944 & INSERM 1427, Institut de Recherche Saint Louis (IRSL), Centre d'Investigation Clinique, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.