USE OF ASC AND ASC-CM TO TREAT ARDS, SARS, AND MERS
Disclosed herein is that the systemic administration of ASC conditioned media diminished LPS-induced lung injury by inhibiting epithelial permeability, neutrophil inflammatory response, and secretion of pro-inflammatory TNFα. It is also shown that ARDS lung is able to retain IV-delivered ASC for a substantial amount of time, with no evidence of the significant cell distribution to other organs at this time point. These findings provide optimization of cell-based and cell-free therapy for the treatment of ARDS, including occurrences of ARDS caused by upper respiratory tract infections such as SARS and MERS.
1 . A method for treating a patient, comprising the step of:
administering at least one therapeutically effective dose of an agent selected from the group consisting of: ASC and ASC-CM, to a patient,
wherein the patient is afflicted with ARDS and wherein the patient is selected from the group consisting of: human and animal.
2 . The method according to claim 1 , wherein ARDS is caused by an upper respiratory tract infection caused by at least one coronavirus selected from the group consisting of: SARS-CoV and MERS-CoV.
3 . The method according to claim 1 , where the therapeutically effective dose of the agent is administered intravenously.
4 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 10,000 Daltons.
5 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 50,000 Daltons.
6 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 60,000 Daltons.
7 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 70,000 Daltons.
8 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 80,000 Daltons.
9 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 100,000 Daltons.
10 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of ASC-CM, the ASC-CM comprising material have a molecular weight of greater than about 150,000 Daltons.
11 . The method according to claim 1 , wherein the patient is administered therapeutically effective dose of a fraction of ASC-CM, comprised of exosomes.
12 . The method according to claim 1 , wherein the patient is administered a therapeutically effective dose of a fraction of ASC-CM, comprised of exosomes concentrated by any of filtration, centrifugation, or precipitation and resuspension.
13 . The method according to claim 4 , wherein the ASC-CM is administered intravenously.
14 . The method according to claim 4 , wherein the ASC-CM is administered by aspirating the material into at least one lung of the patient.
15 . The method according to claim 13 , wherein the dose of ASC-CM administered intravenously is about 0.1 ml/kg to about 2.0 ml/kg, of 100× concentrate of ASC-CM.
16 . The method according to claim 13 , wherein the dose of ASC-CM administered intravenously is about 0.5 ml/kg to about 1.0 ml/kg, of 100× concentrate of ASC-CM.
17 . The method according to claim 1 , wherein the dose of ASC administered intravenously is about 1×10 6 cells/kg to about 1×10 8 cells/kg.
18 . The method according to claim 1 , wherein the dose of ASC administered intravenously is about 1×10 7 cells/kg.
19 . The method according to claim 4 , further comprising the step of formulating ASC-CM material to avoid heat sensitivity.
20 . The method according to claim 4 , further comprising the Step of formulating ASC-CM material to avoid exosome sensitivity.