MSC EVs in Dystrophic Epidermolysis Bullosa

Inclusion Criteria:

1. The first 2 subjects must be 18 years or older at the time of signing the informedconsent. If approved by the SRC, additional subjects (after the first 2 subjects)may be 6 years or older at the time of signing the informed consent; otherwiseadditional subjects must be 18 years or older until such time it is considered bythe SRC as appropriate to lower the age limit to 6 years.

2. Subjects who have a confirmed diagnosis of DEB as determined by electron microscopy,immunomapping, or genetic testing. Subjects with severe DEB (e.g., RDEB patientswith absent Col VII/no anchoring fibrils) and milder forms of DEB (e.g., RDEBpatients with reduced Col VII and/or anchoring fibril levels) will be eligible.

3. Subjects who have one or more active wounds (unroofed EB erosions) each between 10and 50 cm2 on arms, legs, or trunk.

4. Females of childbearing potential must have a negative urine or serum pregnancy testat screening and agree to continue use of an acceptable form of birth controlthroughout the duration of the study. Acceptable forms of birth control includeoral, implant, injectable, and transdermal contraceptives; an intrauterine device;or other forms considered acceptable by the investigator.

5. Subjects or guardian of subjects who are under the age of 18 years must be capableof giving signed informed consent as described in Appendix 1, which includescompliance with the requirements and restrictions listed in the informed consentform (ICF) and in this protocol.

6. Subjects must be willing to comply with the protocol requirements.

7. Subjects must be accessible for wound treatments and assessment visits.

8. Subjects must have a negative urine test for drugs of abuse at the screening visit.

9. Female subjects willing to minimize the risk of inducing pregnancy for the durationof the clinical study and follow-up period.

10. A female subject is eligible to participate if she is not pregnant (i.e. has anegative urine pregnancy result at the Screening Visit and on Day 1), and at leastone of the following conditions applies:

11. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3

12. Or a WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during theintervention and follow-up period

Note: Reference to Appendix 3 can be located in the protocol

Exclusion Criteria:

1. The subject has clinical evidence of systemic infection.

2. The subject has a history or bone marrow transplantation.

3. The subject has evidence of autoimmune disease, including insulin-dependentdiabetes.

4. The subject has wounds that are considered by the investigator as likely to healwithin 1 month after standard therapy.

5. The subject has clinical evidence of an active infection at the wound site.

6. The subject has evidence of significant wound healing before treatment (i.e., ≥ 20%closure of wound during the first month observation period treatment).

7. The subject has a wound that extends across the fingers, toes, pubic or perineumregion.

8. The subject has a severe medical condition, such as malignancy (including skincancer), a life expectancy of < 2 years, or severe cardiopulmonary disease thatrestricts ambulation to the clinical facility.

9. The subject has a history of coagulopathy.

10. The subject currently uses systemic steroids or immunosuppressive agents.

11. The subject is allergic to human albumin, streptomycin, or penicillin.

12. The subject is a potential recipient of tissue or organ transplantation.

13. The subject has a current history of alcohol or substance abuse or has a history ofalcohol or substance abuse that required treatment within the previous 12 months.

14. The subject has a positive test result for human immunodeficiency virus (HIV) atscreening.

15. The subject has a history of poor compliance or unreliability.

16. Females who are pregnant, nursing, or planning a pregnancy during theirparticipation in the study.