Back to chapter

10.12:

๋งŒ๋Šฅ์ค„๊ธฐ์„ธํฌ

JoVE Core
Molekularbiologie
This content is Free Access.
JoVE Core Molekularbiologie
Induced Pluripotent Stem Cells

Sprachen

Teilen

์œ ๋„๋‹ค๋Šฅ์„ฑ ์ค„๊ธฐ์„ธํฌ(iPCS)๋Š”์„ฑ์ˆ™ํ•˜๊ณ  ๋ถ„ํ™”๋œ ์„ธํฌ์ด๋‹ค์ด๋ฅผํ…Œ๋ฉด ํ”ผ๋ถ€ ์„ธํฌ๋ฅผ ์‹คํ—˜์‹ค์—์„œ ์žฌํ”„๋กœ๊ทธ๋žจํ•˜์—ฌ๋ฏธ๋ถ„ํ™”๋œ ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ์™€ ๋น„์Šทํ•˜๊ฒŒ ๋งŒ๋“œ๋Š” ๊ฒƒ์ด๋‹ค์ฆ‰, ์„ธํฌ๊ฐ€ ๋ถ„์—ดํ•˜๊ณ  ๋‹ค๋Šฅ์„ฑ์ด ๋˜์–ด์„œ๋ชจ๋“  ํ˜•ํƒœ์˜ ์„ธํฌ๋ฅผ ์ƒ์„ฑํ•  ์ˆ˜ ์žˆ๋Š” ๊ฒƒ์ด๋‹ค์ด๋ฅผํ…Œ๋ฉด, ๋ง๋ง‰ ์„ธํฌ๋ฅผ ์ด์šฉํ•˜์—ฌ ์†์ƒ๋œ๋ง๋ง‰ ์กฐ์ง์„ ๋Œ€์ฒดํ•˜๋Š” ๊ฒƒ์ฒ˜๋ŸผiPSC๋ฅผ ๋งŒ๋“ค๋ ค๋ฉด, ํ”ผ๋ถ€ ์„ฌ์œ ๋ชจ์„ธํฌ ๊ฐ™์ด ์„ฑ์ˆ™ํ•œ์„ธํฌ๋ฅผ ํ™˜์ž์—์„œ ๋–ผ์–ด๋‚ด์„œ ๋ฐฐ์–‘์‹œํ‚จ๋‹ค๊ทธ๋ฆฌ๊ณ  ๋ณดํ†ต์€ ์ „์‚ฌ ์ธ์ž ์œ ์ „์ž๋ฅผ๋ฐ”์ด๋Ÿฌ์Šค ๋ฒกํ„ฐ๋กœ ์„ธํฌํ•ต์— ์ „๋‹ฌํ•˜๋Š”๋ฐ๊ฑฐ๊ธฐ์—์„œ ์œ ์ „์ฒด์— ํ†ตํ•ฉ๋œ๋‹ค๊ทธ๋‹ค์Œ ์ „์‚ฌ ์ธ์ž๋Š” ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ์— ์˜ํ•˜์—ฌํ‘œ์ถœ๋˜๋Š” ์œ ์ „์ธ์ž๋ฅผ ์ผœ์„œํšจ๊ณผ์ ์œผ๋กœ ํƒˆ๋ถ„ํ™” ์‹œํ‚ค๊ณ ๋‹ค๋Šฅ์„ฑ ์ƒํƒœ๋กœ ๋˜๋Œ๋ ค ๋†“๋Š”๋‹ค์ด์ œ๋Š” ์„ธํฌ๊ฐ€ ๋ถ„์—ดํ•˜๊ณ , ์ด์ƒ์ ์œผ๋กœ๋Š” ๋ฐฐ์–‘์•ก์—์„œ๊ตฌ์ฒด์ ์ธ ์„ธํฌ ์œ ํ˜•์„ ๋งŒ๋“ค๋„๋ก ์ง€์‹œํ•  ์ˆ˜ ์žˆ๋‹ค์ƒˆ๋กœ์šด ์„ธํฌ๋Š” ๊ทธ ๋‹ค์Œ์— ํ™˜์ž์—๊ฒŒ ๋‹ค์‹œ์ด์‹์„ ํ•ด์„œ ์†์ƒ์ด๋‚˜ ์งˆ๋ณ‘์„ ์น˜๋ฃŒํ•˜๋Š”๋ฐ๊ฑฐ๋ถ€ ์œ„ํ—˜์ด ๊ฑฐ์˜ ์—†๋Š” ์ด์œ ๋Š”๊ทธ ์„ธํฌ๊ฐ€ ํ™˜์ž ์ž์‹ ์˜ ์„ธํฌ์—์„œ ๋‚˜์˜จ ๊ฒƒ์ด๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค

10.12:

๋งŒ๋Šฅ์ค„๊ธฐ์„ธํฌ

์ค„๊ธฐ์„ธํฌ(stem cell)๋Š” ๋ถ„์—ดํ•˜์—ฌ ๋‹ค์–‘ํ•œ ์ข…๋ฅ˜์˜ ์„ธํฌ๋ฅผ ์ƒ์„ฑํ•˜๋Š” ๋ฏธ๋ถ„ํ™” ์„ธํฌ์ž…๋‹ˆ๋‹ค. ์ผ๋ฐ˜์ ์œผ๋กœ ํŠน์ • ์„ธํฌ ์œ ํ˜•์œผ๋กœ ๋ถ„ํ™”ํ•œ ์„ธํฌ๋Š” ๋” ๋ถ„์—ดํ•˜์ง€ ์•Š์Šต๋‹ˆ๋‹ค(post-mitotic). ๊ทธ๋Ÿฌ๋‚˜ ๊ณผํ•™์ž๋“ค์€ ์ด ์„ฑ์ˆ™ ์„ธํฌ๋ฅผ ์žฌํ”„๋กœ๊ทธ๋žจํ•˜์—ฌ “ํƒˆ๋ถ„ํ™””ํ•˜๊ณ  ํŠน์ˆ˜ํ™”๋˜์ง€ ์•Š์€ ์ฆ์‹ ์ƒํƒœ๋กœ ๋Œ๋ฆฌ๋Š” ๋ฐฉ๋ฒ•์„ ๋ฐœ๊ฒฌํ–ˆ์Šต๋‹ˆ๋‹ค. ์ด ์„ธํฌ๋“ค์€ ๋˜ํ•œ ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ(embryonic stem cell)์™€ ๊ฐ™์ด ๋งŒ๋Šฅ(pluripotent)์ด๋ฉฐ, ๋ชจ๋“  ์„ธํฌ ์œ ํ˜•์„ ์ƒ์‚ฐํ•  ์ˆ˜ ์žˆ์–ด์„œ ์œ ๋„ ๋งŒ๋Šฅ์ค„๊ธฐ์„ธํฌ(induced pluripotent stem cell, ์ค„์—ฌ์„œ iPSC)๋ผ๊ณ  ๋ถ€๋ฆ…๋‹ˆ๋‹ค.

iPSC ์„ธํฌ๋Š” ํŠน์ • ์„ธํฌ ์œ ํ˜•์ด ํ•„์š”ํ•œ ํ™˜์ž(์˜ˆ๋ฅผ ๋“ค์–ด, ํ™ฉ๋ฐ˜โ€‹โ€‹๋ณ€์„ฑ(macular degeneration)์œผ๋กœ ๋ง๋ง‰์ด ์†์ƒ๋œ ์‚ฌ๋žŒ)๊ฐ€ ์‹ ์ฒด์˜ ๋‹ค๋ฅธ ์„ธํฌ ์œ ํ˜•์—์„œ ์ƒ์„ฑ๋œ ํ•„์š” ์„ธํฌ๋ฅผ ์ด์‹์„ ๋ฐ›์„ ์ˆ˜ ์žˆ๊ธฐ ๋•Œ๋ฌธ์— ์˜ํ•™์—์„œ ํ™œ์šฉ๋  ์ž ์žฌ์ ์ธ ๊ฐ€์น˜๊ฐ€ ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๊ฒƒ์„ ์ž๊ฐ€์ด์‹(autologous transplantation)์ด๋ผ๊ณ  ํ•˜๋Š”๋ฐ, ๊ฐœ์ธ ๊ฐ„์— ์กฐ์ง์ด ์ด์‹๋  ๋•Œ ๋ฐœ์ƒํ•  ์ˆ˜ ์žˆ๋Š” ์ด์‹ ๊ฑฐ๋ถ€๋ฐ˜์‘์˜ ์œ„ํ—˜์„ ์ค„์—ฌ์ค๋‹ˆ๋‹ค.

๊ณผ์ •

iPSC๋ฅผ ๋งŒ๋“ค๊ธฐ ์œ„ํ•ด ํ”ผ๋ถ€ ์„ฌ์œ ์•„์„ธํฌ(fibroblast)๋‚˜ ์‚ฌ๋žŒ์˜ ํ˜ˆ์•ก ์„ธํฌ์™€ ๊ฐ™์€ ์„ฑ์ˆ™ํ•œ ์„ธํฌ๋ฅผ ๋ฐฐ์–‘ํ•ด ์ฆ์‹์‹œํ‚ต๋‹ˆ๋‹ค. ์ด์–ด์„œ ๋ฐ”์ด๋Ÿฌ์Šค ๋ฒกํ„ฐ(vector)๋ฅผ ์‚ฌ์šฉํ•ด ์—ฌ๋Ÿฌ ์ „์‚ฌ ์ธ์ž(transcription factor) ์œ ์ „์ž๊ฐ€ ์„ธํฌ๋กœ ์ „๋‹ฌ๋˜๊ณ , ์ „์‚ฌ ์ธ์ž ๋‹จ๋ฐฑ์งˆ์€ ์„ธํฌ์˜ ๋‚ด๋ถ€ ์ฒด๊ณ„๋ฅผ ์‚ฌ์šฉํ•˜์—ฌ ๋ฐœํ˜„๋ฉ๋‹ˆ๋‹ค. ์ „์‚ฌ ์ธ์ž๋Š” ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ์—์„œ ๋ฐœํ˜„๋˜๋Š” ์—ฌ๋Ÿฌ ์œ ์ „์ž์˜ ๋ฐœํ˜„์„ ์ผœ์„œ ์„ธํฌ๋“ค์„ ๋ถ„ํ™”๋˜์ง€ ์•Š๊ณ  ์ฆ์‹ํ•˜๋Š” ๋งŒ๋Šฅ ์ƒํƒœ๋กœ ๋˜๋Œ๋ฆฝ๋‹ˆ๋‹ค.

iPSC๊ฐ€ ์ •๋ง๋กœ ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ์™€ ๊ฐ™์€์ง€ ์—ฌ๋ถ€๋Š” ์—ฌ์ „ํžˆ ์—ฐ๊ตฌ๋˜๊ณ  ์žˆ์ง€๋งŒ, ๋ฐฐ์•„ ์ค„๊ธฐ์„ธํฌ์™€ ์œ ์‚ฌํ•œ ๊ฒƒ์œผ๋กœ ๋ณด์ด๋ฉฐ, ์„ธ ๊ฐ€์ง€ ๋ฐฐ์—ฝ์—์„œ ๋ชจ๋‘ ์„ธํฌ๋ฅผ ์ƒ์„ฑํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ๊ณผํ•™์ž๋“ค์€ ๋‹ค๋ฅธ ์ข…๋ฅ˜์˜ ์ค„๊ธฐ์„ธํฌ์™€ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ ํ•„์š”ํ•œ ์„ธํฌ ์œ ํ˜•์ด ์ ์ ˆํ•œ ์–‘์œผ๋กœ ์ƒ์„ฑ๋  ์ˆ˜ ์žˆ๋„๋ก iPSC๋กœ๋ถ€ํ„ฐ ํŠน์ • ์„ธํฌ ์œ ํ˜•์˜ ๋ถ„ํ™”๋ฅผ ํšจ์œจ์ ์œผ๋กœ ์ด‰์ง„ํ•˜๋Š” ๋ฐฉ๋ฒ•์„ ์—ฐ๊ตฌํ•˜๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค.

์กฐ๊ธฐ ์ž„์ƒ ์‹œํ—˜

์ฒซ ๋ฒˆ์งธ ์ž„์ƒ ์‹œํ—˜์€ iPSC์—์„œ ํŒŒ์ƒ๋œ ๋ง๋ง‰ ์„ธํฌ๋ฅผ ๋…ธํ™” ์—ฐ๊ด€ ํ™ฉ๋ฐ˜๋ณ€์„ฑ์„ ๊ฐ€์ง„ ํ™˜์ž์—๊ฒŒ ์ด์‹ํ–ˆ์Šต๋‹ˆ๋‹ค. ์ดํ›„ ์—ฌ๋Ÿฌ iPSC ์ž„์ƒ์‹œํ—˜์€ ํŒŒํ‚จ์Šจ๋ณ‘, ์‹ฌ์žฅ๋ณ‘, ๊ทธ๋ฆฌ๊ณ  ์ฒ™์ˆ˜์†์ƒ์˜ ์น˜๋ฃŒ๋ฅผ ์œ„ํ•ด ์Šน์ธ๋˜์—ˆ์Šต๋‹ˆ๋‹ค. ํ™˜์ž๋กœ๋ถ€ํ„ฐ ์ฑ„์ทจํ•˜์—ฌ iPSC๋กœ ๋ณ€ํ™˜ํ•œ ์„ธํฌ๋“ค๋„ ์‹คํ—˜์‹ค์—์„œ ์งˆ๋ณ‘์„ ์—ฐ๊ตฌํ•˜๋Š” ๋ฐ ์‚ฌ์šฉ๋˜๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ์ผ๋ฐ˜์ ์œผ๋กœ iPSC๋Š” ๊ณผํ•™ ์—ฐ๊ตฌ๋ฅผ ์œ„ํ•œ ๋˜ ๋‹ค๋ฅธ ์ค„๊ธฐ์„ธํฌ์˜ ์›์ฒœ์„ ์ œ๊ณตํ•ฉ๋‹ˆ๋‹ค.

Suggested Reading

Hamazaki, Takashi, Nihal El Rouby, Natalie C. Fredette, Katherine E. Santostefano, and Naohiro Terada. “Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine.” Stem Cells (Dayton, Ohio) 35, no. 3 (March 2017): 545–50. [Source].