Name: reprogramming mature cells into stem cells
Uploaded: 2019-03-11T09:21:22.000Z
Duration: 1 min 13 s
Channel: JoVE

- [Verteller] Geïnduceerde pluripotente stamcellen, iPSC's, zijn rijpe, gedifferentieerde cellen, zoals huidcellen, die in het laboratorium worden geherprogrammeerd om vergelijkbaar te zijn met ongedifferentieerde embryonale stamcellen. Dat wil zeggen, ze delen en zijn pluripotent, in staat om elk celtype in het lichaam te produceren. Bijvoorbeeld, netvliescellen die gebruikt kunnen worden om beschadigd netvliesweefsel te vervangen.

Om iPSC's te creëren, worden volwassen cellen, zoals huidfibroblasten, bij een patiënt afgenomen en op kweek gezet. Vervolgens worden genen voor transcriptiefactoren meestal door virale vectoren in de celkernen gebracht, waar ze in het genoom worden opgenomen. De transcriptiefactoren schakelen dan genen aan die tot uitdrukking komen in embryonale stamcellen, waardoor ze in feite worden gededifferentiëerd en in een pluripotente staat worden gebracht.

De cellen kunnen zich nu delen en bij voorkeur worden gestuurd om een specifiek celtype in kweek te produceren. De nieuwe cellen kunnen dan terug in de patiënt worden getransplanteerd om schade of ziekte te behandelen met een minimaal risico op afstoting omdat ze afkomstig zijn van de eigen cellen van de patiënt.

geïnduceerde pluripotente stamcellen

Induced Pluripotent Stem Cells

Stamcellen zijn ongedifferentieerde cellen die zich delen en verschillende soorten cellen produceren. Normaal gesproken zijn cellen die zich hebben gedifferentieerd tot een specifiek celtype postmitotisch–dat wil zeggen dat ze zich niet langer delen. Wetenschappers hebben echter een manier gevonden om deze volwassen cellen te herprogrammeren, zodat ze ‘de-differentiëren’. en terugkeren naar een niet-gespecialiseerde, proliferatieve staat. Deze cellen zijn ook pluripotent zoals embryonale stamcellen – in staat om alle celtypen te produceren – en worden daarom geïnduceerde pluripotente stamcellen (iPSC's) genoemd.

iPSC's zijn potentieel waardevol in de geneeskunde, omdat een patiënt die een bepaald celtype nodig heeft –bijvoorbeeld iemand met een beschadigd netvlies als gevolg van maculaire degeneratie– een transplantatie kan krijgen van de benodigde cellen, gegenereerd uit een ander celtype in zijn eigen lichaam. Dit wordt autologe transplantatie genoemd en vermindert het risico op transplantaatafstoting dat kan optreden wanneer weefsels tussen individuen worden getransplanteerd.

<h4>Het proces</h4>

Om iPSC's te maken, worden volwassen cellen zoals huidfibroblasten of bloedcellen van een persoon in cultuur gekweekt. Vervolgens worden genen voor meerdere transcriptiefactoren in de cellen afgeleverd met behulp van een virale vector, en worden de transcriptiefactoreiwitten tot expressie gebracht met behulp van de machinerie van de cel. De transcriptiefactoren zetten vervolgens vele andere genen aan die tot expressie worden gebracht door embryonale stamcellen, waardoor de cellen terugkeren naar een ongedifferentieerde, proliferatieve en pluripotente staat.

Er wordt nog onderzocht of iPSC's echt gelijkwaardig zijn aan embryonale stamcellen, maar ze lijken op elkaar en kunnen cellen produceren uit alle drie de kiemlagen van het lichaam. Net als bij andere soorten stamcellen leren wetenschappers hoe ze de differentiatie van specifieke celtypen uit iPSC's efficiënt kunnen bevorderen, zodat de benodigde celtypen in voldoende hoeveelheden kunnen worden geproduceerd.

<h4>Vroege klinische onderzoeken</h4>

Bij de eerste klinische proef werden retinale cellen afkomstig van iPSC's getransplanteerd in patiënten met leeftijdsgebonden maculaire degeneratie. Sindsdien zijn verschillende iPSC klinische onderzoeken goedgekeurd voor de behandeling van de ziekte van Parkinson, hartaandoeningen en dwarslaesie. Cellen die van patiënten worden afgenomen en in iPSC's worden omgezet, worden ook gebruikt om hun ziekten in het laboratorium te bestuderen. Over het algemeen bieden iPSC's een andere bron van stamcellen voor wetenschappelijk onderzoek.

Geïnduceerde pluripotente stamcellen

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell ...

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reprogramming mature cells into stem cells

Reprogramming mature cells into stem cells lets scientists turn specialized cells back into an unspecialized state. These cells are called induced pluripotent stem cells, or iPSCs. Like embryonic stem cells, iPSCs are pluripotent, which means they can form all cell types.

To make iPSCs, researchers start with mature cells such as skin fibroblasts or blood cells. The cells are grown in culture, and genes for several transcription factors are delivered with a viral vector. The cells then make those transcription factor proteins, which switch on other genes that are active in embryonic stem cells and return the cells to a proliferative, undifferentiated, and pluripotent state.

iPSCs may be useful in medicine because they can come from a patient’s own body. For example, cells needed to repair a damaged retina in age-related macular degeneration could be made from that same patient’s cells. This autologous transplantation lowers the risk of transplant rejection that can happen when tissue is moved between different people.

Scientists are still studying whether iPSCs are truly equivalent to embryonic stem cells, but they appear to be similar and can produce cells from all three germ layers. Researchers are also working on ways to direct iPSCs to become specific cell types in efficient amounts. Early clinical trials have used iPSC-derived retinal cells for macular degeneration, and other trials have been approved for Parkinson’s disease, heart disease, and spinal cord injury. Patient cells turned into iPSCs are also helping scientists study disease in the lab.

Reprogramming Mature Cells into Stem Cells

reprogramming-mature-cells-into-stem-cells

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induced pluripotent stem cells

Reprogramming mature cells into stem cells lets scientists turn specialized cells back into an unspecialized state. These cells are called induced pluripotent stem cells, or iPSCs. Like embryonic stem cells, iPSCs are pluripotent, which means they can form all cell types. To make iPSCs, researchers start with mature cells such as skin fibroblasts or blood cells. The cells are grown in culture, and genes for several transcription factors are delivered with a viral vector. The cells then make...

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key terms and concepts

Learn how mature cells are reprogrammed into induced pluripotent stem cells, why iPSCs matter for transplants, and how they are used in research and clinical trials.

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Reprogramming Mature Cells into Stem Cells

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