Fetal Cell Receptors Repertoire (MoreCCR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT06031714

Recruitment Status : Not yet recruiting

First Posted : September 11, 2023

Last Update Posted : September 21, 2023

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Venous Ulcer Sickle Cell Ulcer Diabetic Ulcer Post-partum Women	Other: Saliva sampling Other: Blood sampling Other: Interviews Other: Clinical examination	Not Applicable

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	130 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	"Study of CCR Receptor Overexpression in Fetal Microchimeric Cells: Proof of Concept Before a Potential Clinical Trial"
Estimated Study Start Date :	November 1, 2023
Estimated Primary Completion Date :	April 1, 2026
Estimated Study Completion Date :	November 1, 2026

Arms and Interventions

Arm	Intervention/treatment
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
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
Children	Other: Saliva sampling HLA genotyping. The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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 venous ulcers, diabetes or sickle cell disease,

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06031714

Contacts

Layout table for location contacts

Contact: Sélim ARACTINGI, MD, PHD	00 33 1 58 41 18 13	selim.aractingi@aphp.fr
Contact: Marie Benhammani-Godard	00 33 1 58 41 11 90	marie.godard@aphp.fr

Locations

Layout table for location information

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

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Layout table for investigator information

Study Director:	Sélim ARACTINGI, MD, PHD	Dermatology unit, Cochin Hospital - APHP

More Information

Layout table for additonal information

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT06031714
Other Study ID Numbers:	APHP230731 2023-A00404-41 ( Other Identifier: ANSM )
First Posted:	September 11, 2023 Key Record Dates
Last Update Posted:	September 21, 2023
Last Verified:	September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Microchimerism Foetal stem cells Receptors

Additional relevant MeSH terms:

Layout table for MeSH terms

Varicose Ulcer Ulcer Pathologic Processes Varicose Veins Vascular Diseases	Cardiovascular Diseases Leg Ulcer Skin Ulcer Skin Diseases

To Top