Clinical formulations
Some aspects of this disclosure provide clinical media that support viability, re-plating efficiency, and repopulation capacity of cells and tissues during storage for up to 48 hours or longer. The clinical media provided herein are also useful for clinical irrigation. Cell or tissue preparations comprising a cell population or tissue and a clinical medium as provided herein are also provided, as are methods for generating such preparations. Methods for using the clinical media and cell and tissue preparations provided herein, for example, for administering an effective amount of cells or tissue to a subject in need thereof, are also disclosed.
1. A method for treating a retinal disease, the method comprising
administering, to the eye of a human subject having a retinal disease, an effective amount of a pharmaceutical composition comprising
(a) a population of cells, and
(b) a solution comprising
(i) about 0.1-1.2 mM CaCl 2 , about 0.05-5 mM MgCl 2 , about 1-2.5 mM KCl, about 0.5-2 mM sodium citrate, about 15-17 mM dextrose, and about 125-175 mM NaCl, or
(ii) about 0.5-0.9 mM CaCl 2 , about 0.2-0.4 mM MgCl 2 , about 1.6-2.4 mM KCl, about 0.8-1.2 mM sodium citrate, about 13-19 mM dextrose, and about 116-174 mM NaCl, or
(iii) about 0.008-0.012% CaCl 2 dihydrate, about 0.0048-0.0072% MgCl 2 hexahydrate, about 0.012-0.018% KCl, about 0.028-0.042% sodium citrate dihydrate, about 0.23-0.35% dextrose, and about 0.68-1.02% NaCl.
2. The method of claim 1 , wherein the solution comprises about 0.9 mM CaCl 2 , about 0.3 mM MgCl 2 , about 2 mM KCl, about 1.2 mM sodium citrate, about 15 mM dextrose, and about 145 mM NaCl.
3. The method of claim 1 , wherein the solution comprises about 0.01% CaCl 2 dihydrate, about 0.006% MgCl 2 hexahydrate, about 0.015% KCl, about 0.035% sodium citrate dihydrate, at least 0.25% dextrose, and about 0.85% NaCl.
4. The method of claim 1 , wherein the solution further comprises a polymer present at a concentration of about 0.01-0.05% w/v.
5. The method of claim 1 , wherein the polymer is present at a concentration of about 0.05% w/v.
6. The method of claim 1 , wherein the polymer is hyaluronic acid or a salt or a solvate thereof.
7. The method of claim 1 , wherein the polymer is sodium hyaluronate.
8. The method of claim 1 , wherein the solution further comprises sodium acetate.
9. The method of claim 1 , wherein the solution can be
(a) stored for at least 48 hours at 25° C. without measurable precipitation of solutes and/or measurable loss of the capability of the solution to support survival and viability of cells stored in the solution, and/or
(b) stored for at least 48 hours at 2-8° C. without measurable precipitation of solutes and/or measurable loss of the capability of the solution to support survival and viability of cells stored in the solution.
10. The method of claim 1 , wherein the pharmaceutical composition is stored for at least 4, at least 6, at least 12, at least 24, at least 36, or at least 48 hours prior to administration to the eye of the subject.
11. The method of claim 1 , wherein the retinal disease is rod or cone dystrophy, retinal degeneration, retinal detachment, retinal dysplasia, Angioid streaks, retinitis pigmentosa, choroideremia, diabetic retinopathy, macular degeneration, myopic macular degeneration, retinal atrophy, pathologic myopia, Leber congenital amaurosis, glaucoma, or Stargardt disease.
12. The method of claim 1 , wherein the population of cells is a population of retinal pigment epithelial (RPE) cells.
13. The method of claim 1 , wherein the population of cells is a population of retinal ganglion cells, or a population of retinal progenitor cells, or a population of retinal pigment epithelial (RPE) progenitor cells, or a population of iris pigmented epithelial (IPE) cells, or a population of neural cells, or a population of mesenchymal cells, or a population of mesenchymal stem cells.
14. The method of claim 1 , wherein the population of cells is a population of photoreceptor cells.
15. The method of claim 1 , wherein the population of cells is a population of corneal cells.
16. A method for treating a human subject in need of cellular therapy comprising
(a) reconstituting a population of cells with a solution comprising
(i) about 0.1-1.2 mM CaCl 2 , about 0.05-5 mM MgCl 2 , about 1-2.5 mM KCl, about 0.5-2 mM sodium citrate, about 15-17 mM dextrose, and about 125-175 mM NaCl, or
(ii) about 0.5-0.9 mM CaCl 2 , about 0.2-0.4 mM MgCl 2 , about 1.6-2.4 mM KCl, about 0.8-1.2 mM sodium citrate, about 13-19 mM dextrose, and about 116-174 mM NaCl, or
(iii) about 0.008-0.012% CaCl 2 dihydrate, about 0.0048-0.0072% MgCl 2 hexahydrate, about 0.012-0.018% KCl, about 0.028-0.042% sodium citrate dihydrate, about 0.23-0.35% dextrose, and about 0.68-1.02% NaCl, and
(b) administering an effective amount of the reconstituted population of cells to a subject in need thereof.
17. The method of claim 16 , wherein the population of cells is a population of photoreceptor cells.
18. The method of claim 16 , wherein the population of cells is reconstituted after cryopreservation.
19. The method of claim 16 , wherein reconstituting a population of cells comprises contacting a population of cells with the solution.
20. The method of claim 16 , wherein reconstituting a population of cells comprises diluting a population of cells with the solution.
21. The method of claim 16 , wherein the population of cells is a population of retinal pigment epithelial cells (RPE) cells.
22. The method of claim 16 , wherein the population of cells is a population of retinal ganglion cells, or a population of retinal progenitor cells, a population of hematopoietic stem or progenitor cells, a population of neural stem or progenitor cells, a population of neural cells, a population of astrocytes or astrocyte progenitors, a population of glial or glial cell progenitor cells, or a population of pancreatic cells.
23. The method of claim 16 , wherein the subject has rod or cone dystrophy, retinal degeneration, retinal detachment, retinal dysplasia, Angioid streaks, retinitis pigmentosa, choroideremia, diabetic retinopathy, macular degeneration, myopic macular degeneration, retinal atrophy, pathologic myopia, Leber congenital amaurosis, glaucoma, or Stargardt disease.
24. The method of claim 16 , wherein the solution comprises
(a) about 0.9 mM CaCl 2 , about 0.3 mM MgCl 2 , about 2 mM KCl, about 1.2 mM sodium citrate, about 15 mM dextrose, and about 145 mM NaCl, or
(b) about 0.01% CaCl 2 dihydrate, about 0.006% MgCl 2 hexahydrate, about 0.015% KCl, about 0.035% sodium citrate dihydrate, at least 0.25% dextrose, and about 0.85% NaCl.
25. The method of claim 16 , wherein the solution further comprises
(a) a polymer present at a concentration of about 0.01-0.05% w/v, and/or
(b) sodium acetate.
26. The method of claim 25 , wherein the polymer is
(a) present at a concentration of about 0.05% w/v, and/or
(b) hyaluronic acid or a salt or a solvate thereof, and/or
(c) sodium hyaluronate.
27. The method of claim 16 , wherein the population of cells is a population of corneal cells.
28. The method of claim 16 , wherein the population of cells is a population of mesenchymal cells.
29. The method of claim 16 , wherein the population of cells is a population of mesenchymal stem cells (MSCs).