A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

نویسندگان

  • Seonmi Park
  • Andreia Gianotti-Sommer
  • Francisco Javier Molina-Estevez
  • Kim Vanuytsel
  • Nick Skvir
  • Amy Leung
  • Sarah S. Rozelle
  • Elmutaz Mohammed Shaikho
  • Isabelle Weir
  • Zhihua Jiang
  • Hong-Yuan Luo
  • David H.K. Chui
  • Maria Stella Figueiredo
  • Abdulraham Alsultan
  • Amein Al-Ali
  • Paola Sebastiani
  • Martin H. Steinberg
  • Gustavo Mostoslavsky
  • George J. Murphy
چکیده

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

سلول‏های بنیادی پرتوان القایی از تولید تا کاربرد: مقاله مروری

Embryonic stem cells are pluripotent stem cells which have the ability to indefinitely self-renew and differentiate into all differentiated cells of the body. Regarding their two main properties (unlimited self-renewal and multi-lineage differentiation), these cells have various biomedical applications in basic research and cell based therapy. Because the transplantation of differentiated cells...

متن کامل

Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines

The human genome with all its ethnic variations contributes to differences in human development, aging, disease, repair, and response to medical treatments and is an exciting area of research and clinical study. The availability of well-characterized ethnically diverse stem cell lines is limited and has not kept pace with other advances in stem cell research. Here we derived xenofree ethnically...

متن کامل

Large-Scale Expansion of Human Embryonic and Induced Pluripotent Stem Cells for Cell Therapy Applications

Successful isolation, derivation and culturing of human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem (hiPSCs) cells in laboratory scale has opened new horizones for cell therapy applications such as tissue engineering and regenerative medicine. However, most of the cell therapy protocols using these unique cells require large number of ...

متن کامل

ارزیابی روش‌های تولید سلول‌های بنیادی پرتوان ـ مروری کوتاه

Background and Objectives: Nowadays, cell therapy is one of the most important and promising strategies in the treatment of diseases. Unique capabilities of stem cells caused them to be used in both research and treatment as a valuable resource in basic science and medical researches. The use of stem cells has been limited due to the related ethical problems. One of the major concerns of sci...

متن کامل

Fingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors

Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017