Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

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Abstract

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

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Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis.

Minoru Takasato, Pei X Er, Han S Chiu … (2015)

The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.

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Nephron organoids derived from human pluripotent stem cells model kidney development and injury

Ryuji Morizane, Albert Lam, Benjamin S Freedman … (2015)

Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.

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The incredible journey: From megakaryocyte development to platelet formation

Kellie R. Machlus, Joseph E. Italiano (2013)

Circulating blood platelets are specialized cells that prevent bleeding and minimize blood vessel injury. Large progenitor cells in the bone marrow called megakaryocytes (MKs) are the source of platelets. MKs release platelets through a series of fascinating cell biological events. During maturation, they become polyploid and accumulate massive amounts of protein and membrane. Then, in a cytoskeletal-driven process, they extend long branching processes, designated proplatelets, into sinusoidal blood vessels where they undergo fission to release platelets. Given the need for platelets in many pathological situations, understanding how this process occurs is an active area of research with important clinical applications.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Cell Biol

Journal ID (iso-abbrev): Int J Cell Biol

Journal ID (publisher-id): IJCB

Title: International Journal of Cell Biology

Publisher: Hindawi Publishing Corporation

ISSN (Print): 1687-8876

ISSN (Electronic): 1687-8884

Publication date (Print): 2016

Publication date (Electronic): 19 July 2016

Volume: 2016

Electronic Location Identifier: 6940283

Affiliations

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Author notes

*Ranjeet Singh Mahla: ranjeet@ 123456iiserb.ac.in

Academic Editor: Paul J. Higgins

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Ranjeet Singh Mahla http://orcid.org/0000-0002-5525-8442

Article

DOI: 10.1155/2016/6940283

PMC ID: 4969512

PubMed ID: 27516776

SO-VID: 16ecf619-b7f5-4642-b0f7-b39a05383370

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This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 13 March 2016

Date accepted : 5 June 2016

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Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

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Stress signalling in stem cells

Most cited references 109

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis.

Nephron organoids derived from human pluripotent stem cells model kidney development and injury

The incredible journey: From megakaryocyte development to platelet formation

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