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Researchers say they have generated induced pluripotent stem cells (iPSCs) that can differentiate into multiple lineages of functional lymphocytes.
The team noted that lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived iPSCs could potentially be used to treat hematologic disorders, but no one has generated “truly functional” L-HSCs from iPSCs.
So the researchers set out to determine whether iPSCs have the inherent potential to generate multiple lineages of functional, terminally differentiated lymphocytes.
They described this work in Stem Cells and Development.
The researchers said they used tetraploid embryo complementation to provide a normal environment for the differentiation of L-HSCs from iPSCs and embryonic stem cells (ESCs). The team then compared lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice.
The researchers found that iPSC-derived lymphocytes expressed normal levels of major histocompatibility complex-I. Levels were comparable in iPSC-derived lymphocytes, ESC-derived lymphocytes, and lymphocytes from the control mice.
In addition, iPSC-derived lymphocytes were able to differentiate into multiple cell types—CD4+ T cells, CD8+ T cells, regulatory T cells, B cells, and natural killer cells.
Lymphocytes generated from iPSCs and lymphocytes generated from ESCs had the same capacity as lymphocytes from the control mice to proliferate and secrete chemical signals, such as cytokines.
All 3 types of lymphocytes proliferated under allogeneic stimulation but not under syngeneic stimulation. And the researchers found similar levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF, and IFN-γ in iPSC, ESC, and C57BL/6 lymphocyte culture supernatants.
The team also found that lymphocytes generated by iPSC-derived bone marrow cells could repopulate the hematopoietic systems of lethally irradiated recipient mice.
The iPSC bone marrow cells proved as effective as ESC-derived bone marrow cells and wild-type bone marrow cells. All 3 types of cells negated lymphocyte storage exhaustion in the spleen and peripheral blood.
In addition, there were no major phenotypic or behavioral abnormalities in any of the mice more than 1 month after cell transplantation.
The researchers said this work shows that truly functional lymphocytes can be generated from iPSCs, and it supports the clinical application of iPSC technology to develop treatments for hematologic disorders. 
Image from the Salk Institute
Researchers say they have generated induced pluripotent stem cells (iPSCs) that can differentiate into multiple lineages of functional lymphocytes.
The team noted that lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived iPSCs could potentially be used to treat hematologic disorders, but no one has generated “truly functional” L-HSCs from iPSCs.
So the researchers set out to determine whether iPSCs have the inherent potential to generate multiple lineages of functional, terminally differentiated lymphocytes.
They described this work in Stem Cells and Development.
The researchers said they used tetraploid embryo complementation to provide a normal environment for the differentiation of L-HSCs from iPSCs and embryonic stem cells (ESCs). The team then compared lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice.
The researchers found that iPSC-derived lymphocytes expressed normal levels of major histocompatibility complex-I. Levels were comparable in iPSC-derived lymphocytes, ESC-derived lymphocytes, and lymphocytes from the control mice.
In addition, iPSC-derived lymphocytes were able to differentiate into multiple cell types—CD4+ T cells, CD8+ T cells, regulatory T cells, B cells, and natural killer cells.
Lymphocytes generated from iPSCs and lymphocytes generated from ESCs had the same capacity as lymphocytes from the control mice to proliferate and secrete chemical signals, such as cytokines.
All 3 types of lymphocytes proliferated under allogeneic stimulation but not under syngeneic stimulation. And the researchers found similar levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF, and IFN-γ in iPSC, ESC, and C57BL/6 lymphocyte culture supernatants.
The team also found that lymphocytes generated by iPSC-derived bone marrow cells could repopulate the hematopoietic systems of lethally irradiated recipient mice.
The iPSC bone marrow cells proved as effective as ESC-derived bone marrow cells and wild-type bone marrow cells. All 3 types of cells negated lymphocyte storage exhaustion in the spleen and peripheral blood.
In addition, there were no major phenotypic or behavioral abnormalities in any of the mice more than 1 month after cell transplantation.
The researchers said this work shows that truly functional lymphocytes can be generated from iPSCs, and it supports the clinical application of iPSC technology to develop treatments for hematologic disorders.
Image from the Salk Institute
Researchers say they have generated induced pluripotent stem cells (iPSCs) that can differentiate into multiple lineages of functional lymphocytes.
The team noted that lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived iPSCs could potentially be used to treat hematologic disorders, but no one has generated “truly functional” L-HSCs from iPSCs.
So the researchers set out to determine whether iPSCs have the inherent potential to generate multiple lineages of functional, terminally differentiated lymphocytes.
They described this work in Stem Cells and Development.
The researchers said they used tetraploid embryo complementation to provide a normal environment for the differentiation of L-HSCs from iPSCs and embryonic stem cells (ESCs). The team then compared lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice.
The researchers found that iPSC-derived lymphocytes expressed normal levels of major histocompatibility complex-I. Levels were comparable in iPSC-derived lymphocytes, ESC-derived lymphocytes, and lymphocytes from the control mice.
In addition, iPSC-derived lymphocytes were able to differentiate into multiple cell types—CD4+ T cells, CD8+ T cells, regulatory T cells, B cells, and natural killer cells.
Lymphocytes generated from iPSCs and lymphocytes generated from ESCs had the same capacity as lymphocytes from the control mice to proliferate and secrete chemical signals, such as cytokines.
All 3 types of lymphocytes proliferated under allogeneic stimulation but not under syngeneic stimulation. And the researchers found similar levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF, and IFN-γ in iPSC, ESC, and C57BL/6 lymphocyte culture supernatants.
The team also found that lymphocytes generated by iPSC-derived bone marrow cells could repopulate the hematopoietic systems of lethally irradiated recipient mice.
The iPSC bone marrow cells proved as effective as ESC-derived bone marrow cells and wild-type bone marrow cells. All 3 types of cells negated lymphocyte storage exhaustion in the spleen and peripheral blood.
In addition, there were no major phenotypic or behavioral abnormalities in any of the mice more than 1 month after cell transplantation.
The researchers said this work shows that truly functional lymphocytes can be generated from iPSCs, and it supports the clinical application of iPSC technology to develop treatments for hematologic disorders.