Contribution of fetal microchimeric cells to maternal wound healing in sickle cell ulcers
Mansour Alkobtawi,
Maria Sbeih,
Karim Souaid,
Qui Trung Ngô,
Dany Nassar,
Hugo Arbes,
Henri Guillet,
Anoosha Habibi,
Pablo Bartolucci,
Mathieu Castela,
Sélim Aractingi,
Bénédicte Oulès
Affiliations
Mansour Alkobtawi
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris
Maria Sbeih
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris
Karim Souaid
Department of Dermatology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France; University Paris Cité, Faculté de Médecine Paris Centre Santé, Paris
Qui Trung Ngô
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris
Dany Nassar
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris, France; Department of Dermatology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France; University Paris Cité, Faculté de Médecine Paris Centre Santé, Paris
Hugo Arbes
Institut de Biologie Intégrative de la Cellule, Genomic structure and Translation Lab, UMR_9198, CEA, CNRS, Université Paris-Saclay, Orsay
Henri Guillet
Department of Internal Medicine, Red Blood Cell Genetic Diseases Unit, Hôpital Mondor, AP-HP. Hôpitaux Universitaires Henri Mondor, Créteil
Anoosha Habibi
Department of Internal Medicine, Red Blood Cell Genetic Diseases Unit, Hôpital Mondor, AP-HP. Hôpitaux Universitaires Henri Mondor, Créteil
Pablo Bartolucci
Department of Internal Medicine, Red Blood Cell Genetic Diseases Unit, Hôpital Mondor, AP-HP. Hôpitaux Universitaires Henri Mondor, Créteil
Mathieu Castela
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris
Sélim Aractingi
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris, France; Department of Dermatology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France; University Paris Cité, Faculté de Médecine Paris Centre Santé, Paris
Bénédicte Oulès
Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris, France; Department of Dermatology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France; University Paris Cité, Faculté de Médecine Paris Centre Santé, Paris
Leg ulcers are a major complication of sickle cell disease (SCD). They are particularly challenging to treat and innovative therapies are needed. We previously showed that the healing of SCD ulcers is delayed because of decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mother are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we investigated whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates refractory SCD ulcers, we showed that the ulcers of post-partum SCD mice healed more quickly than those of virgin mice. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, using several parameters we found that SCD women who had ever had a baby had less of a burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be exploited to promote wound healing in post-partum SCD patients.
