Fetal Cell Receptors Repertoire

Not Applicable

Recruiting

• Conditions: Venous Ulcer; Diabetic Ulcer; Sickle Cell Ulcer; Post-partum Women; Mixed Ulcer
• Interventions: Other: Saliva sampling; Other: Blood sampling; Other: Interviews; Other: Clinical examination

• Registration Number: NCT06031714
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The purpose of this study is to describe the transcriptomic profile of foetal cells in post-partum and more specifically to determine which chemokine receptors are overexpressed in foetal cells in post-partum women with wounds To do so, the investigators will isolate foetal cells from the peripheral blood of healthy controls post partum women as well as from post partum women with skin ulcers and then perform RNA sequencing.

Detailed Description

The aim of regenerative medicine is to repair damaged tissue using different sources of autologous or heterologous stem cells. These cells are then cultured to achieve amplification and differentiation adapted to the cell type of the organ to be repaired. These methods are potentially effective, but involve risks and limitations, in particular the risks of genetic modifications during culture or contamination by residual ES or iPS cells. Immunosuppressive treatment is also necessary if the source of stem cells is allogeneic. Finally, implantation of this type of culture may also be unsuccessful.

Our team is seeking for an alternative strategy to these methods. This relies on the presence of a niche of foetal cells transferred during pregnancy that persist after delivery. In fact, all mammalian pregnancies lead to foetal-maternal cell transfer. The foetal cells -transferred to the maternal circulation- contain different types of stem cells that will remain in the maternal bone marrow and persist there for the rest of the mother's life. The team has shown that in the event of cutaneous wounds in post-gestational mice, a population of CD11b+ CD34+ CD31+ foetal progenitors was recruited from the maternal bone marrow to the cutaneous granulation tissue. These cells over-express the chemokine receptor CCR2 compared with their adult counterparts. Consequently, the injection of low, so-called physiological, doses of the CCL2 chemokine subcutaneously into wounds accelerates normal wound healing and restores delayed healing in two pathological models. This pro-healing activity is linked to the specific recruitment of foetal stem cells to the site of injected wounds. These low doses of CCL2 never affected wound healing in virgin mice, confirming that this type of treatment does not alter the homeostasis of adult cells.

The therapeutic strategy the investigators are proposing, entitled "natural stem therapy", is based on this reservoir of foetal stem cells present in every woman who has had at least one pregnancy, i.e. more than 60% of adult women in western countries. In order to test the validity of this concept, it is important to ascertain the pathways by which foetal cells are chemoattracted in the human species, in particular the CCR2/CCL2 pathway.

Study Timeline

• Study First Submitted: 2023-09-04
• Study First Submitted QC: 2023-09-08
• Study First Posted: 2023-09-11
• Study Start: 2024-02-06
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-08
• Last Update Posted: 2024-04-10
• Primary Completion: 2026-07-01
• Study Completion: 2027-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

Common criteria :

• Adult women,
• Post-partum: having been pregnant for any length of time,
• Having signed a free and informed consent form,
• Primiparous or multiparous,
• Affiliated to a health insurance

Patients :

• Patients with a venous, diabetic or sickle cell ulcer, or mixed ulcer

Control group patients :

• Volunteers,
• Age-matched,
• Without skin ulcers.

There are no specific criteria for children.

Read More

Exclusion Criteria

• Minors (for patients)
• Under court protection, curatorship, guardianship (for patients)
• Immunocompromised patients for any reason whatsoever
• Refusal of consent
• Refusal of blood and/or saliva samples for themselves or a member of their family

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients	Saliva sampling	Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer
Patients	Interviews	Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer
Children	Saliva sampling	-
Patients	Clinical examination	Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer
Patient "Controls group "	Clinical examination	Post-partum women of the same age but without wounds.
Patient "Controls group "	Saliva sampling	Post-partum women of the same age but without wounds.
Patients	Blood sampling	Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer
Patient "Controls group "	Blood sampling	Post-partum women of the same age but without wounds.
Patient "Controls group "	Interviews	Post-partum women of the same age but without wounds.

Primary Outcome Measures

Name	Time	Method
Transcriptomic analysis by single cell sequencing	Month 1 up to month 5	Transcriptomic analysis by single cell RNA sequencing (Smart-seq3 protocol) of fetal cells sorted from peripheral blood

Trial Locations

Locations (1)

Dermatology unit - Cochin Hospital - APHP; 🇫🇷 Paris, Ile De France, France