Prevention and Treatment of Teratoma Formation in Stem Cell-Based Therapies Using Alternating Electric Fields
In the context of a stem cell-based therapy in which differentiated cells are derived from pluripotent stem cells, this application discloses approaches for eliminating residual pluripotent stem cells that may remain in a batch of differentiated progeny cells. This advantageously prevents the formation of teratoma tumors when the differentiated cells are eventually used for the therapy. This can be accomplished by exposing the batch of differentiated progeny cells and the residual pluripotent stem cells to an alternating electric field for a period of time. The frequency and field strength of the alternating electric field are such that the pluripotent stem cells die off as a result of exposure to the alternating electric fields, while the differentiated cells remain substantially unharmed. This results in a purified batch of differentiated progeny cells that is rendered safe for use in the stem cell-based therapy.
1 . A method of preventing iatrogenic teratoma tumors in a stem cell-based cancer therapy by eliminating residual pluripotent stem cells from a batch of differentiated progeny cells, the method comprising:
exposing the batch of differentiated progeny cells and the residual pluripotent stem cells to an alternating electric field for a period of time, the alternating electric field having a frequency and a field strength,
wherein the frequency and field strength of the alternating electric field are such that as a result of being exposed to the alternating electric field for the period of time, the pluripotent stem cells die off, resulting in a purified batch of differentiated progeny cells that is rendered safe for subsequent use in the stem cell-based therapy, and
wherein the frequency and field strength of the alternating electric field are such that the differentiated cells that are exposed to the alternating electric field for the period of time remain substantially unharmed; and
subsequent to the exposing, using the purified batch of differentiated progeny cells to treat the cancer.
2 . The method of claim 1 , wherein the stem cell-based cancer therapy is a stem cell-based therapy for leukemia.
3 . The method of claim 1 , wherein the stem cell-based cancer therapy is a stem cell-based therapy for lymphoma.
4 . A method of eliminating residual pluripotent stem cells from a batch of differentiated progeny cells in order to prevent the formation of teratomas in a stem cell-based therapy, the method comprising:
exposing the batch of differentiated progeny cells and the residual pluripotent stem cells to an alternating electric field for a period of time, the alternating electric field having a frequency and a field strength,
wherein the frequency and field strength of the alternating electric field are such that as a result of being exposed to the alternating electric field for the period of time, the pluripotent stem cells die off, resulting in a purified batch of differentiated progeny cells that is rendered safe for subsequent use in the stem cell-based therapy, and
wherein the frequency and field strength of the alternating electric field are such that the differentiated cells that are exposed to the alternating electric field for the period of time remain substantially unharmed.
5 . The method of claim 4 , wherein the purified batch contains fewer than 100,000 pluripotent stem cells.
6 . The method of claim 4 , wherein the purified batch contains fewer than 10,000 pluripotent stem cells.
7 . The method of claim 4 , wherein the period of time is at least 12 hours.
8 . The method of claim 4 , wherein the period of time is at least 2 days.
9 . The method of claim 4 , wherein the alternating electric field has an orientation that is switched from time to time between at least two different directions during the period of time.
10 . The method of claim 4 , wherein the alternating electric field has a frequency between 50 kHz and 500 kHz.
11 . The method of claim 10 , wherein the alternating electric field has a field strength of at least 1 V/cm.
12 . The method of claim 4 , wherein the alternating electric field has a frequency between 250 kHz and 350 kHz and a field strength of at least 1 V/cm.
13 . The method of claim 4 , wherein the alternating electric field has a frequency between 50 kHz and 500 kHz and a field strength of at least 1 V/cm, and wherein the period of time is at least 12 hours.
14 . The method of claim 4 , wherein the alternating electric field has a frequency between 250 kHz and 350 kHz and a field strength of at least 1 V/cm, and wherein the period of time is at least 3 days.
15 . The method of claim 4 , further comprising, subsequent to the exposing, using the batch of differentiated cells for a therapeutic or diagnostic purpose.
16 . The method of claim 4 , wherein prior to the exposing, the batch of differentiated progeny cells is obtained by expanding pluripotent stem cells and differentiating the expanded pluripotent stem cells into the batch of differentiated progeny cells.
17 . The method of claim 4 , wherein the exposing step is performed in vitro.
18 . The method of claim 4 , wherein the exposing step is performed in vivo.
19 . The method of claim 4 , wherein the pluripotent stem cells comprise one or more of induced pluripotent stem cells, embryonic stem cells, cancer stem cells, and embryonic germ cells.
20 . The method of claim 4 , wherein the differentiated progeny cells are comprised of cardiomyocytes or cardiomyocyte progenitors.
21 . The method of claim 4 , wherein the pluripotent stem cells and the differentiated progeny cells are human cells.