Fetal Cell Receptors Repertoire (MoreCCR)
"Study of CCR Receptor Overexpression in Fetal Microchimeric Cells: Proof of Concept Before a Potential Clinical Trial"
Study Overview
Status
Intervention / Treatment
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
Enrollment (Estimated)
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
-
-
Île-de-France Region
-
Paris, Île-de-France Region, 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
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)
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
|
HLA genotyping.
The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.
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.
V2 and/or V3
V2 and/or V3
|
|
Other: Patient "Controls group "
Post-partum women of the same age but without wounds.
|
HLA genotyping.
The technique should allow to identify, for children's, a paternal HLA antigen not shared with the mothers.
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.
V2 and/or V3
V2 and/or V3
|
|
Other: Children
|
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
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
|
Month 1 up to month 5
|
Collaborators and Investigators
Collaborators
Investigators
- Study Director: Sélim ARACTINGI, MD, PHD, Dermatology unit, Cochin Hospital - APHP
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Vascular Diseases
- Cardiovascular Diseases
- Skin Diseases
- Skin Ulcer
- Varicose Veins
- Leg Ulcer
- Skin and Connective Tissue Diseases
- Varicose Ulcer
- Health Care Quality, Access, and Evaluation
- Investigative Techniques
- Epidemiologic Methods
- Therapeutics
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Data Collection
- Health Care Evaluation Mechanisms
- Quality of Health Care
- Public Health
- Environment and Public Health
- Blood Specimen Collection
- Behavior Control
- Immobilization
- Interviews as Topic
- Phlebotomy
- Restraint, Physical
Other Study ID Numbers
- APHP230731
- 2023-A00404-41 (Other Identifier: ANSM)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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