Fast and Efficient Neural Conversion of Human Hematopoietic Cells

Castaño, Julio; Menéndez, Pablo; Bruzos-Cidón, Cristina; Straccia, Marco; Sousa, Amaia; Zabaleta, Lorea; Vazquez, Nerea; Zubiarrain, Amaia; Sonntag, Kai‐Christian; Ugedo, Luisa; Carvajal‐Vergara, Xonia; Canals, Josep M.; Torrecilla, Rosa Cañada; Sánchez‐Pernaute, Rosario; Giorgetti, Alessandra

doi:10.1016/j.stemcr.2014.10.008

Cited by 33 publications

(27 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For biomedical applications the usage of these cells is inexpedient as this cell source precludes the clinical use for autologous cell replacement therapy. Recently, studies were published that describe the generation of neural precursor cells from more easily accessible tissues, such as hematopoietic cells 43,44 . The successful generation of tripotent neural stem cell lines could be shown for murine blood-derived B cells by the inducible overexpresion of eight transgenes 43 .…”

Section: Discussionmentioning

confidence: 99%

“…The successful generation of tripotent neural stem cell lines could be shown for murine blood-derived B cells by the inducible overexpresion of eight transgenes 43 . Moreover, Castano et al published an approach for induction of neuronal progenitors from human hematopoietic cells using Sox2-and c-myc-Sendai virus 44 . The protocol described enables fast and efficient generation of neural cells from CD133…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Derivation of Adult Human Fibroblasts and their Direct Conversion into Expandable Neural Progenitor Cells

Meyer

Wörsdörfer

Günther

et al. 2015

JoVE

View full text Add to dashboard Cite

Generation of induced pluripotent stem cell (iPSCs) from adult skin fibroblasts and subsequent differentiation into somatic cells provides fascinating prospects for the derivation of autologous transplants that circumvent histocompatibility barriers. However, progression through a pluripotent state and subsequent complete differentiation into desired lineages remains a roadblock for the clinical translation of iPSC technology because of the associated neoplastic potential and genomic instability. Recently, we and others showed that somatic cells cannot only be converted into iPSCs but also into different types of multipotent somatic stem cells by using defined factors, thereby circumventing progression through the pluripotent state. In particular, the direct conversion of human fibroblasts into induced neural progenitor cells (iNPCs) heralds the possibility of a novel autologous cell source for various applications such as cell replacement, disease modeling and drug screening. Here, we describe the isolation of adult human primary fibroblasts by skin biopsy and their efficient direct conversion into iNPCs by timely restricted expression of Oct4, Sox2, Klf4, as well as c-Myc. Sox2-positive neuroepithelial colonies appear after 17 days of induction and iNPC lines can be established efficiently by monoclonal isolation and expansion. Precise adjustment of viral multiplicity of infection and supplementation of leukemia inhibitory factor during the induction phase represent critical factors to achieve conversion efficiencies of up to 0.2%. Thus far, patient-specific iNPC lines could be expanded for more than 12 passages and uniformly display morphological and molecular features of neural stem/progenitor cells, such as the expression of Nestin and Sox2. The iNPC lines can be differentiated into neurons and astrocytes as judged by staining against TUJ1 and GFAP, respectively. In conclusion, we report a robust protocol for the derivation and direct conversion of human fibroblasts into stably expandable neural progenitor cells that might provide a cellular source for biomedical applications such as autologous neural cell replacement and disease modeling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Derivation of Adult Human Fibroblasts and their Direct Conversion into Expandable Neural Progenitor Cells

Meyer

Wörsdörfer

Günther

et al. 2015

JoVE

View full text Add to dashboard Cite

show abstract

“…This methodology is faster but less robust because these induced neurons (iN) have a limited self-renewal capacity. In both approaches, the combination of transcription factors overexpressed to generate a desired cell lineage is of primary importance and summarized in Table 3 [269,270,273,[275][276][277][278][279][280][281][282][283][284][285][286][287][288].…”

Section: Lineage-determining Transcription Factorsmentioning

confidence: 99%

Targeting Alzheimer's disease with gene and cell therapies

et al. 2018

View full text Add to dashboard Cite

Alzheimer's disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein and energy homeostasis and alterations in lipid and cholesterol metabolism. In addition, gene and cell therapies for severe neurodegenerative disorders have recently improved technically in terms of safety and efficiency and have translated to the clinic showing encouraging results. Here, we review broadly current data within the field for potential targets that could modify AD through gene and cell therapy strategies. We envision that not only Aβ will be targeted in a disease-modifying treatment strategy but rather that a combination of treatments, possibly at different intervention times may prove beneficial in curing this devastating disease. These include decreased tau pathology, neuronal growth factors to support neurons and modulation of neuroinflammation for an appropriate immune response. Furthermore, cell based therapies may represent potential strategies in the future.

show abstract

“…Cochlear non-sensory epithelial cells can be reprogrammed to functional neurons by Ascl1 alone or Ascl1 and NeuroD1 [48]. Human blood cells from umbilical cord blood or peripheral blood can be converted to neurons or neural stem cells (iNSCs) by transduction of various transcription factors [49], [50], [51], [52], [53]. Adult human pigmented epidermal-derived melanocytes can be converted into iNSCs by the active intracellular form of Notch1 [54].…”

Section: Many Different Types Of Cells Can Be Converted To Induced Nementioning

confidence: 99%

Induced dopaminergic neurons: A new promise for Parkinson’s disease

Xu¹,

Chu

Jiang

et al. 2017

Redox Biology

View full text Add to dashboard Cite

Motor symptoms that define Parkinson’s disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells. They exhibit functional dopaminergic neurotransmission and relieve locomotor symptoms in animal models of Parkinson’s disease. In this review, we will discuss this recent development and its implications to Parkinson’s disease research and therapy.

show abstract

Fast and Efficient Neural Conversion of Human Hematopoietic Cells

Cited by 33 publications

References 55 publications

Derivation of Adult Human Fibroblasts and their Direct Conversion into Expandable Neural Progenitor Cells

Derivation of Adult Human Fibroblasts and their Direct Conversion into Expandable Neural Progenitor Cells

Targeting Alzheimer's disease with gene and cell therapies

Induced dopaminergic neurons: A new promise for Parkinson’s disease

Contact Info

Product

Resources

About