Compositions and methods for providing hematopoietic function without hla matching

Abstract

The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.

1 . A method for providing hematopoietic function to a human patient in need thereof, comprising administering an expanded human cord blood stem cell sample to the patient, wherein said administering is done without matching the HLA-type of the expanded human cord blood stem cell sample to the HLA-type of the patient, wherein the expanded human cord blood stem cell sample has been subjected to an expansion technique that has been shown to result in an at least 50-fold increase in hematopoietic stem cells or hematopoietic stem and progenitor cells in an aliquot of a human cord blood stem cell sample subjected to the expansion technique, relative to an aliquot of the human cord blood cell stem cell sample prior to being subjected to the expansion technique. 
     
     
         2 . The method of  claim 1 , wherein the hematopoietic stem cells or hematopoietic stem and progenitor cells are CD34 + . 
     
     
         3 . A method for providing hematopoietic function to a human patient in need thereof, comprising:
 a. selecting an expanded human cord blood stem cell sample for administration to the patient, wherein said selecting does not take into account the HLA-type of the sample or the HLA-type of the patient; and   b. administering the selected sample, or an aliquot thereof, to the patient.   
     
     
         4 . The method of  claim 3 , wherein the selecting is from among at least 50 frozen expanded human cord blood stem cell samples. 
     
     
         5 . The method of  claim 1 , wherein the expanded human cord blood stem cell sample is derived from the umbilical cord blood and/or placental blood of a single human at birth. 
     
     
         6 . The method of  claim 1 , wherein the expanded human cord blood stem cell sample is a pool of two or more different expanded human cord blood stem cell samples, each different sample in the pool derived from the umbilical cord blood and/or placental blood of a different human at birth. 
     
     
         7 . The method of  claim 6 , wherein all the samples in the pool are derived from the umbilical cord blood and/or placental blood of humans of the same race. 
     
     
         8 . The method of  claim 6 , where all the samples in the pool are derived from the umbilical cord blood and/or placental blood of humans of the same ethnicity. 
     
     
         9 . The method of  claim 1 , wherein the expanded human cord blood stem cell sample contains at least 75 million viable CD34 +  cells. 
     
     
         10 . The method of  claim 1 , wherein the method further comprises producing said expanded human cord blood stem cell sample by a method comprising expanding ex vivo isolated human cord blood stem cells or stem and progenitor cells obtained from the umbilical cord blood and/or placental blood of a human at birth. 
     
     
         11 . The method of  claim 3 , wherein the expanded human cord blood stem cell sample has been subjected to an expansion technique that has been shown to result in an at least 50-fold increase hematopoietic stem cells or hematopoietic stem and progenitor cells in a human cord blood stem cell sample subjected to the expansion technique, relative to the human cord blood cell stem cell sample prior to being subjected to the expansion technique. 
     
     
         12 . The method of  claim 11 , wherein the hematopoietic stem cells or hematopoietic stem and progenitor cells are CD34 + . 
     
     
         13 . The method of  claim 10 , wherein the expanding step comprises contacting the human cord blood stem cells or stem and progenitor cells with an agonist of Notch function. 
     
     
         14 . The method of  claim 1 , wherein the expanded human cord blood stem cell sample has been subjected to an expansion technique that has been shown to increase the number of SCID repopulating cells in a human cord blood stem cell sample subject to the expansion technique, relative to the human cord blood stem cell sample prior to being subject to the expansion technique. 
     
     
         15 . The method of  claim 11 , wherein the expansion technique has been shown to result in an at least 50-fold increase in CD34 +  cells in an aliquot of a human cord blood stem cell sample subjected to the expansion technique, relative an aliquot of the human cord blood cell stem cell sample prior to being subjected to the expansion technique. 
     
     
         16 . The method of  claim 1  wherein the expanded human cord blood stem cell sample is frozen prior to said administering step, and wherein the method further comprises a step of thawing said sample prior to said administering. 
     
     
         17 . A method for providing hematopoietic function to a human patient in need thereof, comprising:
 (a) enriching for hematopoietic stem cells or hematopoietic stem and progenitor cells from the umbilical cord blood and/or placental blood of one or more humans at birth to produce a population enriched in hematopoietic stem cells or hematopoietic stem and progenitor cells;   (b) expanding ex vivo the population enriched in hematopoietic stem cells or hematopoietic stem and progenitor cells to produce an expanded stem cell sample; and   (c) administering the expanded stem cell sample, or an aliquot thereof, to a human patient in need of hematopoietic function, wherein said administering is done without matching the HLA type of the expanded cell sample to the HLA type of the patient.   
     
     
         18 . The method of  claim 17 , wherein the method further comprises the steps of freezing and thawing the expanded stem cell sample after step (b) and before step (c). 
     
     
         19 . The method of  claim 1 , wherein the patient has pancytopenia or neutropenia. 
     
     
         20 . The method of  claim 19 , wherein the pancytopenia or neutropenia is caused by an intensive chemotherapy regimen, a myeloablative regimen for hematopoietic cell transplantation, or exposure to acute ionizing radiation. 
     
     
         21 . A method of producing a bank of frozen, expanded human cord blood stem cells comprising the following steps in the order stated:
 (a) expanding, ex vivo, human cord blood stem cells present in a population enriched for hematopoietic stem cells or hematopoietic stem and progenitor cells obtained from the umbilical cord blood and/or placental blood of one or more humans at birth to produce an expanded human cord blood stem cell sample;   (b) freezing the expanded human cord blood stem cell sample to produce a frozen expanded human cord blood stem cell sample;   (c) storing the frozen expanded human cord blood stem cell sample; and   (d) repeating steps (a)-(c) at least 50 times to produce a bank of at least 50 stored, frozen expanded human cord blood stem cell samples.   
     
     
         22 . The method of  claim 21 , wherein the hematopoietic stem cells or hematopoietic stem and progenitor cells are derived from the umbilical cord blood and/or placental blood of a single human at birth. 
     
     
         23 . The method of  claim 21 , wherein the method further comprises a step of assigning each frozen expanded human cord blood stem cell sample an identifier that distinguishes the frozen expanded human cord blood stem cell sample from the other frozen expanded stem cell samples. 
     
     
         24 . The method of  claim 23 , wherein the method further comprises a step of storing the identifier in one or more computer databases, wherein said stored identifier is associated with information on the physical location where the frozen expanded human cord blood stem cell sample corresponding to the identifier is stored in said bank. 
     
     
         25 . A blood bank comprising at least 50 units of frozen expanded human cord blood stem cell samples. 
     
     
         26 . A computer-implemented method for selecting a frozen expanded human cord blood stem cell sample for use in providing hematopoietic function to a human patient in need thereof, comprising the following steps performed by a suitably programmed computer:
 (a) selecting an identifier from a plurality of at least 50 identifiers stored in a computer database, each identifier identifying a frozen stored expanded human cord blood stem cell sample derived from the umbilical cord blood and/or placental blood of one or more different humans at birth, wherein the selecting does not take into account the respective HLA types of the stored frozen expanded human cord blood stem cell samples corresponding to the respective identifiers, wherein the selecting is to identify a frozen stored expanded human cord blood stem cell sample for administration of the expanded human cord blood stem cell sample, or an aliquot thereof, identified by said identifier to a human patient in need thereof; and   (b) outputting or displaying the selected identifier.   
     
     
         27 . The method of  claim 26 , wherein the frozen expanded human cord blood stem cell sample is derived from the umbilical cord blood and/or placental blood of a single human at birth. 
     
     
         28 . The computer-implemented method of  claim 26 , wherein the outputting or displaying step further outputs or displays information on the physical location of the expanded human cord blood stem cell sample identified by the identifier. 
     
     
         29 . The computer-implemented method of  claim 26 , wherein the method further comprises implementing robotic retrieval of the identified frozen, expanded, human cord blood stem cell sample. 
     
     
         30 . A computer program product for use in conjunction with a computer system, the computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism comprising:
 (a) executable instructions for selecting an identifier from a plurality of at least 50 identifiers stored in a computer database, each identifier identifying a frozen stored expanded human cord blood stem cell sample derived from the umbilical cord blood and/or placental blood of one or more humans at birth, wherein the selecting does not take into account the respective HLA types of the stored frozen expanded human cord blood stem cell samples corresponding to the respective identifiers, wherein the selecting is to identify a frozen stored expanded human cord blood stem cell sample for administration of the expanded human cord blood stem cell sample, or an aliquot thereof, identified by said identifier to a human patient in need thereof; and   (b) executable instructions for outputting or displaying the selected identifier.   
     
     
         31 . An apparatus comprising:
 a processor;   a memory, coupled to the processor, the memory storing a module, the module comprising:   (a) executable instructions for selecting an identifier from a plurality of at least 50 identifiers stored in a computer database, each identifier identifying a frozen stored expanded human cord blood stem cell sample derived from the umbilical cord blood and/or placental blood of one or more humans at birth, wherein the selecting does not take into account the respective HLA types of the stored frozen expanded human cord blood stem cell samples corresponding to the respective identifiers, wherein the selecting is to identify a frozen stored expanded human cord blood stem cell sample for administration of the expanded human cord blood stem cell sample, or an aliquot thereof, identified by said identifier to a human patient in need thereof; and   (b) executable instructions for outputting or displaying the selected identifier.   
     
     
         32 . The method of  claim 3 , wherein the selecting comprises rejecting expanded human cord blood stem cell samples that do not contain at least 75 million CD34 +  cells. 
     
     
         33 . The method of  claim 3 , wherein the selecting further comprises rejecting expanded human cord blood stem cell samples that contain more than 500,000 CD3 +  cells per kilogram patient weight. 
     
     
         34 . The computer-implemented method of  claim 26 , wherein the selecting comprises rejecting identifiers that identify samples that do not contain at least 75 million CD34 +  cells. 
     
     
         35 . The computer-implemented method of  claim 26 , wherein the selecting further comprises rejecting identifiers that identify samples that contain more than 500,000 CD3 +  cells per kilogram patient weight. 
     
     
         36 . The computer program product of  claim 30 , wherein the executable instructions for selecting comprise instructions for rejecting identifiers that identify samples that do not contain at least 75 million CD34 +  cells. 
     
     
         37 . The computer program product of  claim 30 , wherein the executable instructions for selecting further comprise instructions for rejecting identifiers that identify samples that contain more than 500,000 CD3 +  cells per kilogram patient weight. 
     
     
         38 . The apparatus of  claim 31 , wherein the executable instructions for selecting comprise instructions for rejecting identifiers that identify samples that do not contain at least 75 million CD34 +  cells. 
     
     
         39 . The apparatus of  claim 31 , wherein the executable instructions for selecting further comprise instructions for rejecting identifiers that identify samples that contain more than 500,000 CD3 +  cells per kilogram patient weight. 
     
     
         40 . The method of  claim 1 , which further comprises administering to the human patient one or more samples of thawed, previously cryopreserved red blood cell-depleted, whole human umbilical cord blood/placental blood samples.