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

Induzierte pluripotente Stammzellen, iPSCs, sind reife, differenzierte Zellen wie Hautzellen, die im Labor umprogrammiert werden, um undifferenzierten embryonalen Stammzellen ähnlich zu sein.
 Das heißt, sie teilen sich und sind pluripotent, fähig, jeden Zelltyp im Körper zu produzieren.
 Zum Beispiel Netzhautzellen, mit denen beschädigtes Netzhautgewebe ersetzt werden kann.
 Um iPSCs zu erzeugen, werden reife Zellen wie Hautfibroblasten von einem Patienten entnommen und in Kulturen eingebracht.
 Dann werden typischerweise Gene für Transkriptionsfaktoren durch virale Vektoren in die Zellkerne geliefert, wo sie in das Genom eingebaut werden.
 Die Transkriptionsfaktoren schalten dann Gene ein, die von embryonalen Stammzellen exprimiert werden, die sie effektiv dedifferenzieren und in einen pluripotenten Zustand bringen.
 Die Zellen können sich nun teilen und idealerweise so ausgerichtet werden, dass sie einen bestimmten Zelltyp in der Kultur produzieren.
 Die neuen Zellen könnten dann wieder zurück in den Patienten transplantiert werden, um Schäden oder Krankheiten mit minimalem Abstoßungsrisiko zu behandeln, da sie aus den eigenen Zellen des Patienten stammen.

Hamazaki, Takashi, Nihal El Rouby, Natalie C. Fredette, Katherine E. Santostefano und Naohiro Terada. "Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine." Stem Cells (Dayton, Ohio) 35, Nr. 3 (März 2017): 545–50. [<a href="https://doi.org/10.1002/stem.2570" target="__blank">Quelle</a>].

induzierte pluripotente stammzellen

Induced Pluripotent Stem Cells

Stammzellen sind undifferenzierte Zellen, die sich teilen und unterschiedliche Zelltypen produzieren. Normalerweise befinden sich Zellen, die sich zu einem bestimmten Zelltyp differenziert haben, in einem post-mitotischen Zustand. Das bedeutet, dass sie sich nicht mehr teilen. Die Wissenschaftler haben jedoch einen Weg gefunden, diese reifen Zellen umzuprogrammieren, so dass sie sich wieder zurück differenzieren in einen nicht-spezialisierten, proliferativen Zustand. Diese Zellen sind wie embryonale Stammzellen ebenfalls pluripotent. Sie sind dazu in der Lage, alle Zelltypen zu produzieren und man nennt sie daher induzierte pluripotente Stammzellen (iPSCs).
 
 In der Medizin sind iPSCs theoretisch wertvoll, da ein Patient, der einen bestimmten Zelltyp benötigt. Zum Beispiel könnte ein Patient, der eine durch Makuladegeneration beschädigte Netzhaut hat, eine Transplantation der benötigten Zellen erhalten, welche von einem anderen Zelltyp aus seinem Körper entwickelt wurden. Dies wird autologe Transplantation genannt und reduziert das Risiko einer Transplantatabstoßung, welche bei der Transplantation von Gewebe zwischen Individuen auftreten kann.
 
 <h4>Der Prozess</h4>
 
 Um iPSCs zu erzeugen, werden reife Zellen wie Fibroblasten der Haut oder Blutzellen einer Person in einer Kultur gezüchtet. Dann werden Gene für mehrere Transkriptionsfaktoren mit Hilfe eines viralen Vektors in die Zellen eingeschleust. Die Transkriptionsfaktoren werden dann in der Zelle exprimiert. Die Transkriptionsfaktoren schalten dann viele andere Gene ein, die in embryonalen Stammzellen exprimiert werden. Dadurch kehren die Zellen in einen undifferenzierten, proliferativen und pluripotenten Zustand zurück.
 
 Es wird noch untersucht, ob iPSCs wirklich äquivalent zu embryonalen Stammzellen sind. Sie scheinen aber ähnlich zu sein und können Zellen aus allen drei Keimblättern des Körpers produzieren. Wie bei anderen Stammzelltypen lernen die Wissenschaftler, wie sie die Differenzierung bestimmter Zelltypen aus iPSCs effizient fördern können, so dass die benötigten Zelltypen in ausreichender Menge produziert werden können.
 
 <h4>Frühe klinische Studien</h4>
 
 Die erste klinische Studie erforschte die Transplantation von Netzhautzellen die aus iPSCs hergestellt wurden in Patienten mit altersbedingter Makuladegeneration. Seitdem wurden mehrere klinische Studien für die Behandlung von Parkinson, Herzkrankheiten und Rückenmarksverletzungen mit iPSCs zugelassen. Zellen, die von Patienten entnommen und in iPSCs umgewandelt wurden, werden auch zur Untersuchung ihrer Krankheiten im Labor verwendet. Im Allgemeinen stellen iPSCs eine weitere Quelle von Stammzellen für die wissenschaftliche Forschung dar.

Induzierte pluripotente Stammzellen

Stammzellen sind undifferenzierte Zellen, die sich teilen und verschiedene Zelltypen produzieren. Normalerweise werden Zellen, die sich zu einer bestimmten Zelle ...

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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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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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