Modified donor organs

Abstract

A repaired ex vivo organ suitable for transplantation in a human, said repaired ex vivo organ having undergone ex vivo organ perfusion for a maintenance period, wherein said organ had been assessed as being unsuitable for transplantation into a human before the maintenance period and was determined to be suitable for transplantation after the maintenance period.

1 . A repaired ex vivo lung for transplantation into a human recipient, comprising:
 (i) a substantially bloodless perfusate at body temperature comprising:
 (a) methylprednisolone, 
 (b) cilastatin and imipenem, and/or 
 (c) heparin, 
 and 
   (ii) exogenous stem cells that ameliorate injury or inflammation in the ex vivo lung, wherein the lung is from a human donor and wherein the exogenous stem cells are from a source other than the human donor and a source other than the human recipient.   
     
     
         2 . The repaired ex vivo lung of  claim 1 , further comprising (iii) an exogenous transgene. 
     
     
         3 . The repaired ex vivo lung of  claim 2 , wherein the exogenous transgene is in a replication deficient adenoviral vector (serotype 5) under the control of a cytomegalovirus promoter. 
     
     
         4 . The repaired ex vivo lung of  claim 2 , wherein the exogenous transgene encodes a cytokine. 
     
     
         5 . The repaired ex vivo lung of  claim 4 , wherein the exogenous transgene encodes IL-10. 
     
     
         6 . The repaired ex vivo lung of  claim 4 , wherein the exogenous transgene decreases inflammation in the lung by decreasing the level of IL-1β, IL-8 or IL-6 concentrations in the lung compared to a corresponding lung that does not contain the transgene. 
     
     
         7 . The repaired ex vivo lung of  claim 1 , wherein the lung further comprises (a) stable pulmonary vascular resistance, (b) stable dynamic compliance and (c) stable peak respiratory pressure. 
     
     
         8 . The repaired ex vivo lung of  claim 1 , wherein the lung further comprises a partial pressure of arterial oxygen to fraction of inspired oxygen (PO 2 :FIO 2 ) ratio of between about 414 mm Hg and about 443 mm Hg. 
     
     
         9 . The repaired ex vivo lung for transplantation of  claim 1 , wherein the repaired ex vivo lung comprises (a) stable pulmonary vascular resistance of about 200 dynnes/s/cm5, (b) stable dynamic compliance of about 50 ml/cm H 2 O and (c) stable peak respiratory pressure of about 15 cm H 2 O. 
     
     
         10 . The repaired ex vivo lung for transplantation of  claim 1 , wherein the repaired ex vivo lung comprises at least one of antibiotics, beta-agonists, and/or anti-inflammatory agents. 
     
     
         11 . The repaired ex vivo lung for transplantation of  claim 1 , wherein the ex vivo lung was repaired from a Maastricht Category III or a Maastricht Category IV damaged lung. 
     
     
         12 . The repaired ex vivo lung of  claim 11 , further comprising (iii) an exogenous transgene. 
     
     
         13 . The repaired ex vivo lung of  claim 12 , wherein the exogenous transgene is in a replication deficient adenoviral vector (serotype 5) under the control of a cytomegalovirus promoter. 
     
     
         14 . The repaired ex vivo lung of  claim 12 , wherein the exogenous transgene encodes a cytokine. 
     
     
         15 . The repaired ex vivo lung of  claim 14 , wherein the exogenous transgene encodes IL-10. 
     
     
         16 . The repaired ex vivo lung of  claim 14 , wherein the exogenous transgene decreases inflammation in the lung by decreasing the level of IL-1β, IL-8 or IL-6 concentrations in the lung compared to a corresponding lung that does not contain the transgene. 
     
     
         17 . The repaired ex vivo lung for transplantation of  claim 11 , wherein the repaired ex vivo lung further comprises (a) stable pulmonary vascular resistance, (b) stable dynamic compliance and (c) stable peak respiratory pressure. 
     
     
         18 . The repaired ex vivo lung of  claim 11 , wherein the lung further comprises a partial pressure of arterial oxygen to fraction of inspired oxygen (PO 2 :FIO 2 ) ratio of between about 414 mm Hg and about 443 mm Hg. 
     
     
         19 . The repaired ex vivo lung for transplantation of  claim 11 , wherein the repaired ex vivo lung comprises (a) stable pulmonary vascular resistance of about 200 dynnes/s/cm5, (b) stable dynamic compliance of about 50 ml/cm H 2 O and (c) stable peak respiratory pressure of about 15 cm H 2 O. 
     
     
         20 . The repaired ex vivo lung for transplantation of  claim 11 , wherein the repaired ex vivo lung comprises at least one of antibiotics, beta-agonists, and/or anti-inflammatory agents. 
     
     
         21 . The repaired ex vivo lung for transplantation of  claim 11 , wherein the ex vivo lung was repaired from an uncontrolled Maastricht category IV damaged lung.