IMMUNOCOMPATIBLE CHORIONIC MEMBRANE PRODUCTS
Provided herein is a placental product comprising an immunocompatible chorionic membrane. Such placental products can be cryopreserved and contain viable therapeutic cells after thawing. The placental product of the present invention is useful in treating a patient with a tissue injury (e.g. wound or burn) by applying the placental product to the injury. Similar application is useful with ligament and tendon repair and for engraftment procedures such as bone engraftment.
1 . A preserved chorionic membrane comprising viable cells native to the chorionic membrane,
wherein the viable cells comprise two or more of mesenchymal stem cells (MSCs), stromal cells, and fibroblast cells, and
wherein the preserved chorionic membrane is immunocompatible and substantially free of CD14+ macrophages, trophoblasts, vascularized tissue, vascularized tissue-derived immunogenic cells, and immunogenic maternal cells.
2 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises an extracellular matrix that is native to the chorionic membrane and one or more therapeutic factors native to the chorionic membrane.
3 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane releases less than 420 pg/ml of TNF-a.
4 . The preserved chorionic membrane of claim 1 , wherein the immunogenic maternal cells are maternal dendritic cells, maternal leukocytes, or combinations thereof.
5 . The preserved chorionic membrane of claim 1 , wherein at least about 70% of the cells native to the chorionic membrane are viable.
6 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises about 5,000 per cm 2 to about 50,000 per cm 2 stromal cells.
7 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises fibroblasts present in an amount of about 50% to about 90% of the total cells.
8 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises MSCs in an amount of about 5% to about 30%.
9 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises MMP-9 and TIMP-1.
10 . The preserved chorionic membrane of claim 9 , wherein a ratio of MMP-9 to TIMP-1 is from about 7-10 to 1.
11 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises insulin-like growth factor binding protein-1 and adiponectin.
12 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane comprises a whole or partial basement membrane, a whole or partial reticular layer, or a whole or portion combination thereof.
13 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane has a thickness of 40 to 400 micrometers.
14 . The preserved chorionic membrane of claim 1 , wherein the preserved chorionic membrane was previously frozen.
15 . A method of treating a skin wound, the method comprising topically applying to the skin wound a placental product comprising the preserved chorionic membrane of claim 1 .
16 . The method of claim 15 , wherein the skin wound is selected from a chronic wound, an ulcer, a diabetic ulcer, a foot ulcer, a diabetic foot ulcer, a venous ulcer, a venous leg ulcer, a leg ulcer, a pressure ulcer, a burn, a thermal burn, a chemical burn, a partial thickness burn, or a full thickness burn.
17 . The method of claim 15 , wherein the skin wound is selected from a laceration, a scrape, an incision, a puncture, a wound caused by a projectile, an epidermal wound, a dermal wound, a surgical wound, an acute wound, a congenital wound, a toxic epidermal necrolysis, an epidermolysis bullosa, or a pyoderma gangrenosum.
18 . A method of grafting a tissue, the method comprising:
applying the preserved chorionic membrane of claim 1 to at least a portion of a tissue graft; and
attaching the preserved chorionic membrane and the tissue graft to a biological substrate.
19 . The method of claim 18 , wherein the preserved chorionic membrane promotes healing or attachment of the tissue graft to the biological substrate.
20 . The use of claim 18 , wherein the tissue graft comprises skin, cartilage, ligament, tendon, periosteum, perichondrium, synovium, fascia, mesenter, or sinew.