# US 2025/0024832 A1 · Immune-reduced cross-circulation circuit > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0024832 A1 - Document ID: US20250024832A1 - Status: Published application - Kind: A1 - Application number: 18/684,418 - Filed: 2022-08-19 - Published: 2025-01-23 - Earliest claimed: 2021-08-20 - Assignees: Vanderbilt University - Applicants: Vanderbilt University - Inventors: Wei K. Wu; Matthew Bacchetta; Sophoclis Alexopoulos; John W. Stokes; Rei Ukita; Yatrik J. Patel - Web page: https://patentgrep.com/patent/US20250024832A1 ## CPC - A01N 1/143: for organ perfusion - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS ## Abstract A system for maintaining immune separation between an extracorporeal organ and a bioreactor includes an organ chamber holding an extracorporeal organ and a cross-circulation circuit connecting the extracorporeal organ with the bioreactor. The cross-circulation circuit can direct the flow of perfusate therebetween. The bioreactor may include an allogeneic or xenogeneic host organism. for example a swine host. The cross-circulation circuit comprises at least one semipermeable membrane configured to establish an immunologic barrier to maintain separation between the immune responses of the bioreactor and the extracorporeal organ and to maintain physiologic stability of the bioreactor and the extracorporeal organ. The immune-reduced cross-circulation circuit may improve extracorporeal organ viability for research and transplant purposes. ## Claims ### Claim 1 A system comprising: an organ chamber configured to hold an extracorporeal organ; and a cross-circulation circuit configured to connect the extracorporeal organ and a bioreactor and direct the flow of perfusate therebetween, wherein the cross-circulation circuit comprises at least one semipermeable membrane configured to establish an immunologic barrier to maintain separation between immune responses of the bioreactor and immune responses of the extracorporeal organ and to maintain physiologic stability of the bioreactor and the extracorporeal organ. ### Claim 2 (depends on 1) The system of claim 1, wherein the bioreactor is a host organism. ### Claim 3 The system of 2, wherein the host organism is allogeneic or xenogeneic to the extracorporeal organ. ### Claim 4 (depends on 1) The system of claim 1, wherein the cross-circulation circuit comprises an H loop comprising the bioreactor, an O loop comprising the extracorporeal organ, and an immune separation loop maintaining immune response separation between the H loop and the O loop, wherein the H loop, the O loop, and the immune separation loop interface via the at least one semipermeable membrane. ### Claim 5 (depends on 1) The system of claim 1, wherein the at least one semipermeable membrane prevents immune compromising compounds from flowing therethrough. ### Claim 6 The system of 5, wherein the immune compromising compounds comprise inflammatory molecules, antibodies, and immune effector cells. ### Claim 7 The system of 5 wherein the at least one semipermeable membrane comprises a plurality of pores configured to permit non-immune compromising compounds to pass through the cross-circulation circuit based on sizes of the plurality of pores. ### Claim 8 The system of 5, wherein the non-immune compromising compounds comprise electrolytes, hormones, substrates, and small proteins. ### Claim 9 The system of 1, wherein the extracorporeal organ is at least one of a liver, a lung, a kidney, a heart, a limb, skin, or a tissue substrate. ### Claim 10 The system of 1, wherein the immune response is an innate immune response or an adaptive immune response. ### Claim 11 A cross-circulation circuit comprising: an H loop comprising a bioreactor; an O loop comprising an extracorporeal organ, wherein the extracorporeal organ is housed in an organ chamber; and an immune separation loop comprising: a first interface with the H loop comprising a first semipermeable membrane, a second interface with the O loop comprising a second semipermeable membrane, wherein the first semipermeable membrane and the second semipermeable membrane are configured to maintain separation between immune responses of the H loop and the O loop, and at least one pump configured to direct flow through at least one of the H loop, the O loop, and the immune separation loop. ### Claim 12 The cross-circulation circuit of 11, wherein at least one of blood, a non-blood oxygen carrier, an acellular solution, and a crystalloid solution flows through at least one of the H loop, the O loop, and the immune separation loop. ### Claim 13 The cross-circulation circuit of 11, wherein the H loop, the O loop, and the immune separation loop each comprise a different perfusate. ### Claim 14 The cross-circulation circuit of 11, wherein the first membrane and the second membrane are configured to prevent immune compromising components from flowing through the first interface and/or the second interface. ### Claim 15 The cross-circulation circuit of 14, wherein the immune compromising components comprise inflammatory molecules, antibodies, and immune effector cells. ### Claim 16 The system of 11, wherein the first semipermeable membrane and the second semipermeable membrane each comprise a plurality of pores configured to permit non-immune comprising compounds in the perfusate to pass through based on sizes of the plurality of pores. ### Claim 17 The system of 16, wherein the non-immune compromising compounds comprise electrolytes, hormones, substrates, and small proteins. ### Claim 18 The cross-circulation circuit of 11, wherein the bioreactor comprises a host organism of a different species than the extracorporeal organ and the immune separation loop provides an immunologic barrier between the host organism and the extracorporeal organ to prevent xeno-immune injury of the extracorporeal organ. ### Claim 19 A method comprising: establishing a cross-circulation circuit between a bioreactor and an extracorporeal organ in an organ chamber, wherein the cross-circulation circuit comprises: an H loop comprising the bioreactor, an O loop comprising the extracorporeal organ, an immune separation loop, and at least one pump configured to direct flow through at least one of the H loop, the O loop, and the immune separation loop; directing a flow of perfusate between the bioreactor in the H loop and the extracorporeal organ in the O loop through the immune separation loop, wherein the immune separation loop comprises: a first interface with the H loop comprising a first semipermeable membrane, and a second interface with the O loop comprising a second semipermeable membrane; and maintaining viability of the extracorporeal organ using the first semipermeable membrane and the second semipermeable membrane, wherein the first semipermeable membrane and the second semipermeable membrane are configured to maintain separation between immune responses within the H loop and the O loop. ### Claim 20 (depends on 19) The method of claim 19, wherein the perfusate enters and exits the extracorporeal organ and the bioreactor through cannulations of at least one vein and/or at least one artery in each of the extracorporeal organ and the bioreactor. ### Claim 21 The method of 19, wherein the first membrane and the second membrane are configured to prevent immune compromising components from flowing through. ### Claim 22 The method of 21, wherein the immune compromising compounds comprise inflammatory molecules, antibodies, and immune effector cells. ### Claim 23 The method of 19, wherein the first semipermeable membrane and the second semipermeable membrane comprises a plurality of pores configured to permit non-immune compromising compounds to pass through based on sizes of the plurality of pores. ### Claim 24 The method of 23, wherein the non-immune compromising compounds comprise electrolytes, hormones, substrates, and small proteins.