Different cells used for reprogramming
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Normal somatic cells
1. Adipose derived stem cells
In 2009, Sun N. and colleagues have shown that induced pluripotent stem cells (iPSCs) can be generated starting from a population of human adipose stem cells (hASCs) by ectopic expression of human Oct4, Sox2, Klf4 and c-Myc transcription factors. They used a double-transduction (days 0 and 2) with individual lentiviruses containing the four genes at a 1 : 1 : 1 : 1 ratio. The process was ~2-fold faster and ~20-fold more efficient than from reprogramming human IMR90 fibroblast. The advantages are: the lipoaspiration for isolating hASCs is simple, fast, safe and give a large quantity of cells, the hASCs can be isolated from patients of all ages (clinical importance) and feeder-free method of derivation has a great clinical applicability for rapid generation of patient-specific and disease-specific iPSCs. ˃ Read More
2. Amniocytes
3. Astrocytes
4. Bone marrow stem cells
5. CD34+ cells from cord blood (CB), peripheral blood (PB) and bone marrow (BM)
In 2011, iPSCs (Tra-1-60+ marker) were generated from mononuclear cells expressing CD34+ markers. These cells were isolated from CB, PB and BM. Transformations were done using an improved EBNA1/OriP plasmid expressing 5 reprogramming factors (Oct4, Sox2, Klf4, c-Myc and Lin28). CB CD34+ cells were transformed using an episomal vector EBNA1/OriP plasmid (pEB-C5) with 5 reprogramming factors (single poly-cistronic unit) and pEB-Tg plasmid. The PB and BM CD34+ cells were transformed to iPSCs by 1-2 episomal vector combinations. BK. Chou and colleagues ˃ Read More
In 2010, Anchan, RN. and colleagues described a system of methods for generating iPSCs from human and mouse amniocytes. Moreover, they proposed to use the amniocytes as feeder layers for maintaining the pluripotency of iPSCs (no zoonotic risk). iPSCs generation was made by transduction (3 days after cells plated) with four Oct4, Sox2, Klf4 and c-Myc or only two Klf4, c-Myc retroviral vectors in absence of feeder layers. The transformation was achieved in 5-7 days with 0.5 % efficiency. The method has many advantages, including that the amniocytes have a early embryonic origin. ˃ Read More
3. Astrocytes
In 2011, mouse astrocytes induced pluripotent stem cells mAsiPSCs were generated by ectopic retroviral expression in different combination of Oct4, Sox2, Klf4 and c-Myc transcription factors. Validation of these iPSCs was made by stem cell markers (AP, Nanog, SSEA-1) and generation of teratomas with cells of all three germ layers. Tian, C and colleagues tested the property of mAsiPSCs and mouse embryonic fibroblast induced pluripotent stem cells (MEFiPSCs) to differentiate in the embryonic bodies and neurons. Finding that mAsiPSCs grew slower and possessed more potential for neuronal differentiation, they suggested that mAsiPSCs retain a ''memory'' of the nervous system. ˃ Read More
4. Bone marrow stem cells
In 2009, Z. Ye and colleagues reported the generation of iPSCs from human cord blood (CB) and adult blood and marrow CD34+ cells. They were generated iPSCs using four classic vectors pMXs-Oct4, pMXs-Sox2, pMXs-Klf4 and pMXs-c-Myc mouse reprogramming factors constructed by laboratory of Dr. Yamanaka. They also obtained iPSCs from peripheral blood (PB) CD34+ cells of adult patients with myeloproliferative disorders (MPDs). ˃ Read More
5. CD34+ cells from cord blood (CB), peripheral blood (PB) and bone marrow (BM)
In 2011, iPSCs (Tra-1-60+ marker) were generated from mononuclear cells expressing CD34+ markers. These cells were isolated from CB, PB and BM. Transformations were done using an improved EBNA1/OriP plasmid expressing 5 reprogramming factors (Oct4, Sox2, Klf4, c-Myc and Lin28). CB CD34+ cells were transformed using an episomal vector EBNA1/OriP plasmid (pEB-C5) with 5 reprogramming factors (single poly-cistronic unit) and pEB-Tg plasmid. The PB and BM CD34+ cells were transformed to iPSCs by 1-2 episomal vector combinations. BK. Chou and colleagues ˃ Read More
6. Circulating T cells
7. Cord blood cells
Cord blood (CB) cells have begun to be used as source of cells for obtaining of iPSCs, because their harvesting methods are less invasive that other types of cells.
In 2009, Giorgetti et al. described the reprogramming of CD133+ CB cells to pluripotency by retroviral transduction of four (OSKM), three (OSK) and two (OS) transcription factors. ˃ Read More
8. Cord blood endothelial cells 9. Cord blood stem cells
10. Dental Pulp Cells
10. Dental Pulp Cells
11. Hepatocytes
12. Keratinocytes
iPSCs were generated from juvenile human primary keratinocytes by retroviral transductions with Oct4, Sox2, Klf4 and c-Myc (1 : 1 : 1 : 1 mixture of retroviruses). The keratinocyte derived iPS (KiPS) cells were generated at least 100-fold more efficient compared with reprogramming of human fibroblast. KiPS cells expressed genes and cell-surface markers characteristic of human embryonic stem (hES) cells, including Nanog, Oct4, Sox2, REX1, CRIPTO, Connexin43, IGF1 receptor, SSEA3, SSEA4, TRA-1-60 and TRA-1-81. In addition, all KiPS cell lines readily differentiated in vitro into endoderm, mesoderm and ectoderm germ layers and generated complex intratesticular teratomas. ˃ Read More
13. Melanocytes
14. Mesenchymal cells
15. Mesenchymal stromal cells
In 2010, mesenchymal stromal induced pluripotent stem cells MSiPSCs were generated from mesenchymal stromal cells (MSCs) derived from human third molar. This transformation was achieved by retroviral transduction of Oct4, Sox2 and Klf4 transcription factors with 30-100-fold higher efficiency compared to other human MSCs and dermal fibroblast. Another group reported the generation of MSiPSCs from mesenchymal-like stem/progenitor cells from dental tissue by transduction with Oct4, Sox2, Klf4, c-Myc or Oct4, Sox2, Nanog, Lin28 factors. Validation of iPSCs was done by morphology, ES markers expression (Oct4, Sox2, Nanog, Rex1, UTF1, UTF3, DPPA2, DPPA4, DPPA5 and telomerase activity), global gene expression, epigenetic status and the ability to differentiate into the cells of the three germ layers. ˃ Read More
16. Mobilised peripheral blood
17. Neural stem cells
Adult mouse neural stem cells (NSCs) and human fetal neural stem cells were used to generate one-factor (1F) iPS cells by overexpression of the transcription factor Oct4 alone. Adult mouse 1F iPS cells are similar to mouse embryonic stem (ES) cells in vitro (differentiation into NSCs, cardiomyocytes and germ cells) and in vivo (teratoma formation and germline transmission). Fetal human 1F iPS cells resemble human embryonic stem (ES) cells in global gene expression profiles, epigenetic status and their pluripotency in vitro and in vivo. ˃ Read More A, B
18. Peripheral blood and bone marrow mononuclear cells
19. Skin fibroblast
In 2006, Takahashi and Yamanaka demonstrated the induction of pluripotent stem (iPS) cells from mouse embryonic or adult fibroblast by introducing four factors, Oct3/4, Sox2, c-Myc and Klf4, under ES cell culture condition. ˃ Read More
In 2007, Yamanaka and colleagues reported the generation of iPS cells from adult human dermal fibroblast with the same four factors: Oct3/4, Sox2, Klf4 and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, telomerase activities and the ability to form teratomas. ˃ Read More Then, several researches have reported the generation of the iPS cells from human adult fibroblasts. ˃ Read More
Actually, dermal skin fibroblasts are the main source for obtaining induced pluripotent stem (iPS) cells. These cells are easily obtained from patients, a single skin biopsy generates enough cells for a transformation and the cells are easily maintained in culture. However, the process efficiency is reduced, 0.05 % when using Yamanaka 4 factors Oct3/4, Sox2, Klf4 and c-Myc (OSKM). In addition, the time required for a transformation is long, 3-4 weeks. ˃ Read More A, B. Yamanaka considered two models, elite and stochastic models, to explain the low efficiency and partial nature of iPS cells generation. ˃ Read More
20. Lung fibroblast
21. Fibroblast-like synoviocytes
22. Oral mucosa fibroblast
21. Fibroblast-like synoviocytes
22. Oral mucosa fibroblast
23. Human gingival fibroblast and periodontal ligament fibroblasts
In 2011, iPSCs were generated from human gingival fibroblasts and periodontal ligament fibroblasts by reprogramming using the retroviral transductions with Yamanaka transcription factors (Oct4, Sox2, Klf4 and c-Myc). Validation was accomplished by identifying embryonic stem cell markers (SSEA4, TG30 and so on), three embryonic cell layers markers and mouse testes in vivo for ability to form teratomas. ˃ Read More
Cancer cells
In 2010, Miyoshi, N. and colleagues studied the correlations that exist between the induction/inhibition of genes (cancer and immature status related) and alterations reported in gastrointestinal cancer cells. For this study, they generated six cancer induced pluripotent stem cells (CiPS): colorectal cancer cells, esophageal cancer, gastric cancer, hepatocellular carcinoma, cholangiocellular carcinoma and teratocarcinoma. For transfection the classic Oct4, Sox2, Klf4 and c-Myc transcriptional factors were used. Cancer cells were transfected with adequate vector (lentiviruses or retroviruses) at a concentration of 4 µg/µl by using lipofectamine. ˃ Read More
Oct4 (O), Sox2 (S), Klf4 (K), c-Myc (M) and Nanog (N) 1. Colorectal cancer cells - OSKM
2. Esophageal - OSKM
3. Gastric cancer - OSKM
4. Hepatocellular carcinoma - OSKM
4. Hepatocellular carcinoma - OSKM
5. Cholangiocellular carcinoma - OSKM
6. Teratocarcinoma - OSKM
Genetic diseases
In 2008, In-Hyun Park and colleagues reported the derivation of human induced pluripotent stem cells iPSCs from patients with a range of human genetic disease (Mendelian or complex inheritance). They used the dermal fibroblasts from patients with adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Gaucher disease (GD), Duchenne type muscular dystrophy (DMD), Becker type muscular dystrophy (BMD), Downs syndrome (DS), Parkinson disease (PD), juvenile (type I) diabetes mellitus (JDM), Huntington disease (HD), Lesch-Nyhan syndrome carrier (LNSc) and the bone marrow mesenchimal cells from Shwachman-Bodian-Diamond syndrome patient (SBDS) (all patients with a prior diagnosis).
Cells were transduced with either four (Oct4, Sox2, Klf4 and c-Myc) or three (Oct4, Sox2 and Klf4) transcription factors. For Lesch-Nyhan syndrome carrier (LNSc) cells transformation, they used five (Oct4, Sox2, Klf4, c-Myc and Nanog) transcription factors. They cloned the cDNA of transcription factors into doxycycline-inducible vector and coinfected with a lentivirus with a reverse tetracycline transactivator. ˃ Read More
Oct4 (O), Sox2 (S), Klf4 (K), c-Myc (M), Nanog (N) and Lin28 (L28)
In 2009, Z. Ye and colleagues were generated iPSCs from peripheral blood (PB) CD34+ cells of adult patients with myeloproliferative disorders (MPDs): polycythemia vera (PV), essential thrombocytosis (ET) primary myelofibrosis (PMF). ˃ Read More
Oct4 (O), Sox2 (S), Klf4 (K), c-Myc (M), Nanog (N) and Lin28 (L28)
1. Adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID) -
OSKM and OSK
2. Carrier state of Lesch-Nyhan syndrome - OSKMN
3. Dyskeratosis congenita - OSKM from fibroblasts ˃ Read more
3. Dyskeratosis congenita - OSKM from fibroblasts ˃ Read more
4. Down syndrome (DS)/trisomy 21 - OSKM and OSK
5. Duchenne (DMB) and Becker muscular dystrophy (BMB) - OSKM and OSK
6. Fanconi anemia - OSKM from fibroblasts ˃ Read more
7. Familial dysautonomia - OSKM from fibroblasts ˃ Read more
6. Fanconi anemia - OSKM from fibroblasts ˃ Read more
7. Familial dysautonomia - OSKM from fibroblasts ˃ Read more
8. Gaucher disease (GD) type III - OSKM and OSK
9. Huntington disease (HD) Video1, - OSKM and OSK
10. Juvenil-onset, type I diabetes mellitus (JDM) - OSKM and OSK
11. Leopard syndrome - OSKM from human dermal fibroblasts ˃ Read more
11. Leopard syndrome - OSKM from human dermal fibroblasts ˃ Read more
12. Parkinson disease (PD) - OSKM and OSK
13. Rett syndrome
13. Rett syndrome
14. Scwachman-Bodian-Diamond syndrome (SBDS) - OSKM and OSK
15. Spinal muscular atrophy - OSNL28 from primary fibroblasts ˃ Read more
15. Spinal muscular atrophy - OSNL28 from primary fibroblasts ˃ Read more
