Methods of analysis of blood from deceased donors
The invention provides cellular compositions that contain CD34 + cells derived from bone marrow of a decease donor and CD3 + cells derived from non-bone marrow of the deceased donor. The compositions are useful to promote mixed chimerism in recipients of solid organ transplants. The invention also provides methods of making and using such compositions. In certain embodiments, the invention further provides methods of analyzing and preparing blood and blood components from a deceased donor for use in compositions of the invention to promote mixed chimerism in solid organ transplant recipients.
1. A method of assessing whether blood derived from a deceased donor is suitable for use in manufacture of a product comprising mature T cells and hematopoietic stem and progenitor cells (HSPCs) to administer to a living recipient, the method comprising:
obtaining blood derived from a deceased donor;
analyzing mature T cells of the blood by comparing a value of a parameter that is an indicator of T cell activation, T cell proliferation, T cell viability, T cell exhaustion, T cell anergy, or T cell apoptosis of the blood obtained from the deceased donor to a value of the parameter of blood obtained from one or more healthy living donors of blood or blood-derived products;
analyzing HSPCs in the blood by comparing the value of a parameter that is an indicator of HSPC apoptosis, HSPC proliferation, or HSPC viability of the blood obtained from the deceased donor to a value of the parameter of blood obtained from one or more healthy living donors of blood or blood-derived products;
determining that the blood obtained from the deceased donor is suitable for use in manufacture of a product comprising mature T cells and HSPCs to administer to a living recipient if the values of the parameters of the blood obtained from the deceased donor are comparable to the values of the parameters of blood obtained from one or more healthy living donors of blood or blood-derived products; and
using material from the analyzed blood derived from the deceased donor in the manufacture of the product.
2. The method of claim 1 , wherein the parameter of HSPC apoptosis is a level of a non-cellular component in the blood from the deceased donor.
3. The method of claim 2 , wherein the non-cellular component comprises a cytokine or chemokine.
4. The method of claim 1 , wherein the material comprises mature T cells.
5. The method of claim 1 , wherein the material comprises HSPCs.
6. The method of claim 1 , wherein the mature T cell parameter is an indicator of T cell activation, T cell proliferation, or T cell viability.
7. The method of claim 1 , wherein the HSPC parameter is an indicator of HSPC proliferation or HSPC viability.
8. A method of assessing whether peripheral blood obtained from a deceased donor is suitable for use in manufacture of a product comprising mature T cells and hematopoietic stem and progenitor cells (HSPCs) to administer to a living recipient, the method comprising:
obtaining peripheral blood from a deceased donor;
analyzing mature T cells of the peripheral blood by comparing a value of a parameter that is an indicator of T cell activation, T cell proliferation, T cell viability, T cell exhaustion, T cell anergy, or T cell apoptosis of the peripheral blood obtained from the deceased donor to a value of the parameter of blood obtained from one or more healthy living donors of blood or blood-derived products;
analyzing HSPCs of the peripheral blood by comparing the value of a parameter that is an indicator of HSPC apoptosis, HSPC proliferation, or HSPC viability of the peripheral blood obtained from the deceased donor to a value of the parameter of blood obtained from one or more healthy living donors of blood or blood-derived products;
determining that the peripheral blood obtained from the deceased donor is suitable for use in manufacture of a product comprising mature T cells and HSPCs to administer to a living recipient if the values of the parameters of the peripheral blood obtained from the deceased donor are comparable to the values of the parameters of blood obtained from one or more healthy living donors of blood or blood-derived products; and
using material from the analyzed peripheral blood obtained from the deceased donor in the manufacture of the product.
9. The method of claim 8 , wherein the mature T cell parameter is an indicator of T cell exhaustion, T cell anergy, or T cell apoptosis.
10. The method of claim 8 , wherein the HSPCs parameter is an indicator of HSPC apoptosis.
11. The method of claim 8 , wherein the parameter of HSPC apoptosis is a level of a non-cellular component in the peripheral blood from the deceased donor.
12. The method of claim 11 , wherein the non-cellular component comprises a cytokine or chemokine.
13. The method of claim 8 , wherein the material comprises mature T cells.
14. The method of claim 8 , wherein the material comprises HSPCs.