Uncovering the origins of a niche

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

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Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

Biomolecules ◽

10.3390/biom10091306 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1306

Author(s):

Ann-Kristin Afflerbach ◽

Mark D. Kiri ◽

Tahir Detinis ◽

Ben M. Maoz

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Types ◽

In Vitro Models ◽

Cell Source ◽

Fundamental Research ◽

Multiple Cell ◽

Vitro Model

The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research.

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Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

Stem Cells International ◽

10.1155/2012/461718 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 100

Author(s):

Hakan Orbay ◽

Morikuni Tobita ◽

Hiroshi Mizuno

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adult Stem Cells ◽

Cell Types ◽

Biological Properties ◽

Clinical Applications ◽

Therapeutic Tool ◽

Adult Tissues ◽

Clinical Benefits ◽

Multiple Cell

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

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Fibronectin Promotes Survival and Migration of Primary Neural Stem Cells Transplanted into the Traumatically Injured Mouse Brain

Cell Transplantation ◽

10.3727/096020198389933 ◽

2002 ◽

Vol 11 (3) ◽

pp. 283-295 ◽

Cited By ~ 98

Author(s):

Matthew C. Tate ◽

Deborah A. Shear ◽

Stuart W. Hoffman ◽

Donald G. Stein ◽

David R. Archer ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cellular Therapy ◽

Cell Types ◽

Survival Times ◽

Germinal Zone ◽

Cortical Contusion ◽

Multiple Cell ◽

And Migration

Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/ FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p < 0.01). At the longer survival times (3 weeks–3 months), 63–76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p < 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

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Small Bowel

10.2310/im.2248 ◽

2017 ◽

Author(s):

Vincent E Mortellaro

Keyword(s):

Innate Immunity ◽

Small Intestine ◽

Immune System ◽

Small Bowel ◽

Key Words ◽

Cell Types ◽

Complex Interaction ◽

Microscopic Anatomy ◽

Motor Complex ◽

Multiple Cell

The small intestine is where multiple cell types combine to achieve the complex interaction between our bodies and ingested material from the outside world. As a highly specialized organ, the small intestine has a role in digestion, absorption of nutrients and electrolytes, and innate immunity to thwart exogenous pathogens and as host to a symbiotic environment where our immune system successfully interacts with a resident microbiome. This review covers the embryology, gross and microscopic anatomy, physiology of nutritional absorption, immune function, and advances in examining new discoveries in the interplay between the host and the resident microbiome. Key words: duodenum, ileum, jejunum, microbiota, midgut, migrating motor complex, nutritional absorption, villi

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Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2005.09.001 ◽

2006 ◽

Vol 40 (1) ◽

pp. 195-200 ◽

Cited By ~ 120

Author(s):

Dinender K. Singla ◽

Timothy A. Hacker ◽

Lining Ma ◽

Pamela S. Douglas ◽

Ruth Sullivan ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Cell Types ◽

Mouse Heart ◽

Multiple Cell ◽

Heart Formation

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Small Bowel

DeckerMed Surgery ◽

10.2310/surg.2248 ◽

2017 ◽

Author(s):

Vincent E Mortellaro

Keyword(s):

Innate Immunity ◽

Small Intestine ◽

Immune System ◽

Small Bowel ◽

Key Words ◽

Cell Types ◽

Complex Interaction ◽

Microscopic Anatomy ◽

Motor Complex ◽

Multiple Cell

The small intestine is where multiple cell types combine to achieve the complex interaction between our bodies and ingested material from the outside world. As a highly specialized organ, the small intestine has a role in digestion, absorption of nutrients and electrolytes, and innate immunity to thwart exogenous pathogens and as host to a symbiotic environment where our immune system successfully interacts with a resident microbiome. This review covers the embryology, gross and microscopic anatomy, physiology of nutritional absorption, immune function, and advances in examining new discoveries in the interplay between the host and the resident microbiome. Key words: duodenum, ileum, jejunum, microbiota, midgut, migrating motor complex, nutritional absorption, villi

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Single-cell transcriptomics to explore the immune system in health and disease

Science ◽

10.1126/science.aan6828 ◽

2017 ◽

Vol 358 (6359) ◽

pp. 58-63 ◽

Cited By ~ 198

Author(s):

Michael J. T. Stubbington ◽

Orit Rozenblatt-Rosen ◽

Aviv Regev ◽

Sarah A. Teichmann

Keyword(s):

Immune System ◽

Single Cell ◽

Immune Cells ◽

Cell Types ◽

Massively Parallel ◽

Antigen Receptors ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Health And Disease ◽

Multiple Cell

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology. Here we provide an overview of the state of single-cell genomics methods and an outlook on the use of single-cell techniques to decipher the adaptive and innate components of immunity.

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Detection, Characterization, and Clinical Application of Mesenchymal Stem Cells in Periodontal Ligament Tissue

Stem Cells International ◽

10.1155/2018/5450768 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Atsushi Tomokiyo ◽

Shinichiro Yoshida ◽

Sayuri Hamano ◽

Daigaku Hasegawa ◽

Hideki Sugii ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Periodontal Ligament ◽

Cell Types ◽

Stem Cell Population ◽

Tooth Root ◽

Detailed Characterization ◽

Self Renewal ◽

Dental Tissues ◽

Multiple Cell

Mesenchymal stem cells (MSCs) are a kind of somatic stem cells that exert a potential to differentiate into multiple cell types and undergo robust clonal self-renewal; therefore, they are considered as a highly promising stem cell population for tissue engineering. MSCs are identified in various adult organs including dental tissues. Periodontal ligament (PDL) is a highly specialized connective tissue that surrounds the tooth root. PDL also contains MSC population, and many researchers have isolated them and performed their detailed characterization. Here, we review the current understanding of the features and functions of MSC population in PDL tissues and discuss their possibility for the application of PDL regeneration.

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A Modular System to Examine Fibroblastic Differentiation of Mesenchymal Stem Cells Under Tensile Loading in Response to Changes in the Extracellular Environment

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53704 ◽

2011 ◽

Author(s):

Johnna S. Temenoff

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tensile Loading ◽

Cell Types ◽

Modular System ◽

Secondary Degeneration ◽

Joint Biomechanics ◽

Multiple Cell ◽

Vitro Model

Hundreds of thousands of injuries to ligaments, tendons or the joint capsule occur in the U.S. each year, resulting in significant reduction of quality of life for many patients [1]. Existing reconstruction techniques for torn tendons/ligaments result in significant morbidity and cannot fully recapitulate the native joint biomechanics, leading to secondary degeneration over time, such as premature osteoarthritis. Thus, tissue-engineered alternatives to current grafts, potentially using stem cells in combination with an appropriate scaffold, are greatly needed. In response, our laboratory is investigating a novel hydrogel system and a custom tensile bioreactor as an in-vitro model to study the formation of both fibrous (ligament) tissue and the ligament-bone interface. In these studies, we examine the effect of tensile loading and the degradability of the surrounding environment on cellular morphology and tendon/ligament extracellular matrix (ECM) production by mesenchymal stem cells (MSCs). In particular, the response of MSCs embedded within hydrogels with varying degrees of susceptibility to degradation by collagenase is explored. In addition, proof-of-principle experiments are presented to extend this system to examine the effect of co-culture of multiple cell types on differentiation of MSCs in a milieu that mimics the bone-ligament insertion.

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