Fetal Cell Receptors Repertoire (MoreCCR)

"Study of CCR Receptor Overexpression in Fetal Microchimeric Cells: Proof of Concept Before a Potential Clinical Trial"

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.

Study Overview

• Status: Recruiting
• Conditions: Venous Ulcer; Diabetic Ulcer; Sickle Cell Ulcer; Post-partum Women; Mixed Ulcer
• Intervention / Treatment: Other: Saliva sampling; Other: Blood sampling; Other: Interviews; Other: Clinical examination

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 Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marie BENHAMMANI-GODARD; Phone Number: 00 33 1 58 41 11 90; Email: marie.godard@aphp.fr
• Study Contact Backup: Name: Sélim ARACTINGI, MD, PHD; Phone Number: 00 33 1 58 41 18 13; Email: selim.aractingi@aphp.fr

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75014
      • Recruiting
      • Dermatology unit - Cochin Hospital - APHP
      • Contact: Sélim ARACTINGI, MD, PhD; Phone Number: 0033 1 58 41 18 13; Email: selim.aractingi@aphp.fr
      • Sub-Investigator: Bénédicte OULES, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients; Patients who have had at least one pregnancy and have a venous ulcer, diabetic ulcer or sickle cell ulcer	Other: Saliva sampling; HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.; Other: Blood sampling; Maternal Blood samples will be incubated with the appropriate antibody, targeting the microchimeric fetal cells of each patient, as well as with a cell viability marker (DAPI). The samples were then be processed through the BD FACS Aria III to sort the fetal cells, The following steps - RNA extraction, quality control, retrotranscription, preparation of the library, sequencing and transcriptomic analysis - will be carried out according to the Smart-seq3 protocol. The data will be sent for in-depth analysis and confirmation of the results. Additional functional experiments may also be carried out.; Other: Interviews; V2 and/or V3; Other: Clinical examination; V2 and/or V3
Other: Patient "Controls group "; Post-partum women of the same age but without wounds.	Other: Saliva sampling; HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.; Other: Blood sampling; Maternal Blood samples will be incubated with the appropriate antibody, targeting the microchimeric fetal cells of each patient, as well as with a cell viability marker (DAPI). The samples were then be processed through the BD FACS Aria III to sort the fetal cells, The following steps - RNA extraction, quality control, retrotranscription, preparation of the library, sequencing and transcriptomic analysis - will be carried out according to the Smart-seq3 protocol. The data will be sent for in-depth analysis and confirmation of the results. Additional functional experiments may also be carried out.; Other: Interviews; V2 and/or V3; Other: Clinical examination; V2 and/or V3
Other: Children	Other: Saliva sampling; HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Sélim ARACTINGI, MD, PHD, Dermatology unit, Cochin Hospital - APHP

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Receptors; Microchimerism; Foetal stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Leg Ulcer; Skin Ulcer; Varicose Veins; Ulcer; Varicose Ulcer
• Other Study ID Numbers: APHP230731; 2023-A00404-41 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No