HC ‐HA/PTX3 from amniotic membrane reverts senescent limbal niche cells to Pax6+ neural crest progenitors to support limbal epithelial progenitors
Reversal of late passaged limbal niche stromal cells to Pax6+ neural crest progenitors by HC ‐HA/PTX3. AbstractQuiescence and self ‐renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for pro per differentiation of limbal and corneal epithelial stem cells. Pax6 haploinsufficiency causes limbal stem cell deficiency, which leads to subsequent corneal blindness. We previously reported tha...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Szu ‐Yu Chen, Yingting Zhu, Yuan Zhang, David Hsu, Scheffer C.G. Tseng Tags: REGENERATIVE MEDICINE Source Type: research

Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy
In this study, we treated a rat controlled cortical impact model of TBI with a combination of two cell therapies: human regulatory T cells (Treg) expanded from umbilical cord blood and human mesenchymal stro mal cells (MSC) isolated from adipose tissue. We found that a sequential staggered delivery of Treg and MSC significantly reduced proliferation of microglia indicating a reduction in neuroinflammation following treatment. AbstractThe inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system. Cell therapies, includ...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Henry W. Caplan, Karthik S. Prabhakara, Naama E. Toledano Furman, Soheil Zorofchian, Akshita Kumar, Cecilia Martin, Hasen Xue, Scott D. Olson, Charles S. Cox Tags: TRANSLATIONAL AND CLINICAL RESEARCH Source Type: research

Metabolic and immune dysfunction of glia in neurodegenerative disorders: Focus on iPSC models
Induced pluripotent stem cells (iPSC) created from fibroblasts or other easily accessible human cells can be differentiated into patient ‐specific glia such as oligodendrocytes, astrocytes and microglia, and grown together with neurons in culture or in vivo for investigating the role and molecular mechanisms of the glial cell in neurodegenerative diseases. AbstractThe research on neurodegenerative disorders has long focused on neuronal pathology and used transgenic mice as disease models. However, our understanding of the chronic neurodegenerative process in the human brain is still very limited. It is increasingly recog...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Taisia R õlova, Šárka Lehtonen, Gundars Goldsteins, Pinja Kettunen, Jari Koistinaho Tags: CONCISE REVIEW Source Type: research

A preview of selected articles
(Source: Stem Cells)
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Stuart P. Atkinson Tags: PREVIEWS Source Type: research

Cover Image
In vitro differentiation analysis of membrane ‐targeted GFP+ (mGFP+) cells isolated from treated 3‐week‐old trigenic mice, showing that mGFP+ cells contribute to the osteoblast lineage, indicating that Tert expression marks skeletal progenitor/stem cells.See Carlone et al. beginning on page296. (Source: Stem Cells)
Source: Stem Cells - February 23, 2021 Category: Stem Cells Tags: COVER IMAGE Source Type: research

Issue Information
(Source: Stem Cells)
Source: Stem Cells - February 23, 2021 Category: Stem Cells Tags: ISSUE INFORMATION Source Type: research

CCAAT/enhancer ‐binding protein beta promotes muscle stem cell quiescence through regulation of quiescence‐associated genes
CCAAT/enhancer ‐binding protein beta (C/EBPβ) promotes muscle satellite cell quiescence. (A) In resting muscle, satellite cells are quiescent and express both PAX7 and C/EBPβ. C/EBPβ promotes the expression of several quiescence‐associated genes includingCav1. (B) Muscle injury drives activation and proliferation of precursors with a concomitant reduction in C/EBP β expression. (C) Low C/EBPβ expression promotes differentiation and muscle repair. (D) Cells that escape differentiation, self‐renew and return to quiescence are C/EBPβ+. AbstractRegeneration of skeletal muscle depends on resident muscle stem cells c...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Neena Lala ‐Tabbert, Hamood AlSudais, François Marchildon, Dechen Fu, Nadine Wiper‐Bergeron Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

Telomerase expression marks transitional growth ‐associated skeletal progenitor/stem cells
In long bones, osteochondral progenitor cells function during rapid bone growth while osteoadipogenic progenitors act during bone maintenance. We showed that mTert is expressed in an age ‐dependent manner and marks growth‐associated osteochondral progenitor cells during transitional growth, a discrete time period between rapid bone growth and bone maintenance. AbstractSkeletal progenitor/stem cells (SSCs) play a critical role in postnatal bone growth and maintenance. Telomerase (Tert) activity prevents cellular senescence and is required for maintenance of stem cells in self ‐renewing tissues. Here we investigated th...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Diana L. Carlone, Rebecca D. Riba ‐Wolman, Luke T. Deary, Alessio Tovaglieri, Lijie Jiang, Dana M. Ambruzs, Benjamin E. Mead, Manasvi S. Shah, Christopher J. Lengner, Rudolf Jaenisch, David T. Breault Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells
Although mesenchymal stem/stromal cells (MSCs) are promising for cell therapy, long ‐term culture leads to MSC senescence with reduced stem cell capacity. We showed that FZD5, which is specifically expressed in immature MSCs, can serve as a stemness indicator. Controlling FZD5 signaling may improve MSC quality and the outcomes of cell therapy. AbstractHuman mesenchymal stem/stromal cells (hMSCs) have garnered enormous interest as a potential resource for cell ‐based therapies. However, the molecular mechanisms regulating senescence in hMSCs remain unclear. To elucidate these mechanisms, we performed gene expression pro...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Seiko Harada, Yo Mabuchi, Jun Kohyama, Daisuke Shimojo, Sadafumi Suzuki, Yoshimi Kawamura, Daisuke Araki, Takashi Suyama, Masunori Kajikawa, Chihiro Akazawa, Hideyuki Okano, Yumi Matsuzaki Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

Satellite cell activation and retention of muscle regenerative potential after long ‐term denervation
Human satellite cells isolated from gluteus maximus muscle denervated>20  years retain the ability to engraft and form new muscle fiber when transplanted intoNOD.Cg ‐Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice, and also reoccupy the anatomic niche. Left: NSG muscle showing human dystrophin (green) and laminin (red). Right: NSG muscle showing costaining of human lamin A/C (red) Pax7 (green). Laminin (grey), 4 ′,6‐diamidino‐2‐phenylindole (DAPI, blue) counterstain. AbstractIrreversible denervation atrophy remains an unsolved clinical problem, and the role of skeletal muscle stem cell (MuSC, satellite cell) depletion ...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Alvin Wong, Steven M. Garcia, Stanley Tamaki, Katharine Striedinger, Emilie Barruet, Scott L. Hansen, David M. Young, Jason H. Pomerantz Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

Dlk1 regulates quiescence in calcitonin receptor ‐mutant muscle stem cells
Calcitonin receptor (CalcR) ‐mutant muscle stem cells ectopically express delta‐like non‐canonical Notch ligand 1 (Dlk1). The Dlk1 expression marks all non‐quiescent muscle stem cells in CalcR‐mutant muscle stem cells. The loss of Dlk1 rescues the impaired quiescent state in CalcR‐mutant muscle stem cells. AbstractMuscle stem cells, also called muscle satellite cells (MuSCs), are responsible for skeletal muscle regeneration and are sustained in an undifferentiated and quiescent state under steady conditions. The calcitonin receptor (CalcR) ‐protein kinase A (PKA)‐Yes‐associated protein 1 (Yap1) axis is on...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Lidan Zhang, Manami Kubota, Ayasa Nakamura, Takayuki Kaji, Shigeto Seno, Akiyoshi Uezumi, Ditte Caroline Andersen, Charlotte Harken Jensen, So ‐ichiro Fukada Tags: Tissue ‐SPECIFIC STEM CELLS Source Type: research

Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions
This study demonstrated that fibroblast derived extracellular vesicle (EV), induced activation of fibroblast, endothelial cell migration, and tube formation in  vitro and also induced, in vivo wound healing by enhancing the collagen formation and maturation, increasing Vascular endothelial growth factor (VEGF) expression, blood vessel formation, and skin appendages induction. These findings uncovered; fibroblast derived EV can be used as potential cell free/EV‐based candidate for wound healing therapies. AbstractExtracellular vesicles (EVs) have been exhibited as promising candidates for delivering endogenous therape...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Eun Jung Oh, Prakash Gangadaran, Ramya Lakshmi Rajendran, Hyun Mi Kim, Ji Min Oh, Kang Young Choi, Ho Yun Chung, Byeong ‐Cheol Ahn Tags: REGENERATIVE MEDICINE Source Type: research

HC ‐HA/PTX3 from amniotic membrane reverts senescent limbal niche cells to Pax6+ neural crest progenitors to support limbal epithelial progenitors
Reversal of late passaged limbal niche stromal cells to Pax6+ neural crest progenitors by HC ‐HA/PTX3. AbstractQuiescence and self ‐renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for pro per differentiation of limbal and corneal epithelial stem cells. Pax6 haploinsufficiency causes limbal stem cell deficiency, which leads to subsequent corneal blindness. We previously reported tha...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Szu ‐Yu Chen, Yingting Zhu, Yuan Zhang, David Hsu, Scheffer C.G. Tseng Tags: REGENERATIVE MEDICINE Source Type: research

Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy
In this study, we treated a rat controlled cortical impact model of TBI with a combination of two cell therapies: human regulatory T cells (Treg) expanded from umbilical cord blood and human mesenchymal stro mal cells (MSC) isolated from adipose tissue. We found that a sequential staggered delivery of Treg and MSC significantly reduced proliferation of microglia indicating a reduction in neuroinflammation following treatment. AbstractThe inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system. Cell therapies, includ...
Source: Stem Cells - February 23, 2021 Category: Stem Cells Authors: Henry W. Caplan, Karthik S. Prabhakara, Naama E. Toledano Furman, Soheil Zorofchian, Akshita Kumar, Cecilia Martin, Hasen Xue, Scott D. Olson, Charles S. Cox Tags: TRANSLATIONAL AND CLINICAL RESEARCH Source Type: research

CRISPR editing of the GLI1 first intron abrogates GLI1 expression and differentially alters lineage commitment
CRISPR/Cas9 genomic editing was used to delete the first intronic region containing six highly conserved GLl1 binding sites. The decreased GLl1 gene expression impacted GLl1 regulatory capacity within the Sonic Hedgehog signaling pathway. The result was a reduced transcriptional activation of upstream and downstream GLl1 targets, which ultimately impacted endodermal, mesodermal, and ectodermal differentiation via downregulation of key genes. AbstractGLI1 is one of three GLI family transcription factors that mediate Sonic Hedgehog signaling, which plays a role in development and cell differentiation. GLI1 forms a positive f...
Source: Stem Cells - February 22, 2021 Category: Stem Cells Authors: Yekaterina Galat, Haigang Gu, Mariana Perepitchka, Robert Taylor, Joon Won Yoon, Xenia A. Glukhova, Xiao ‐Nan Li, Igor P. Beletsky, David O. Walterhouse, Vasiliy Galat, Philip M. Iannaccone Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research