Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion

2021 ◽  
Author(s):  
Yu-Tong Hong ◽  
Jye Yng Teo ◽  
Hojeong Jeon ◽  
Hyunjoon Kong
Keyword(s):  
Paracrine Factor ◽  
Therapeutic Cell ◽  
Factor Secretion

scholarly journals Anti-senescence ion-delivering nanocarrier for recovering therapeutic properties of long-term-cultured human adipose-derived stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeong Hwan Kim ◽  
Gwang-Bum Im ◽  
Sung-Won Kim ◽  
Yu-Jin Kim ◽  
Taekyung Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Efficacy ◽  
Transition Metal Ions ◽  
Response To Treatment ◽  
Adipose Derived Stem Cells ◽  
Related Gene ◽  
Paracrine Factor ◽  
Therapeutic Properties ◽  
Factor Secretion

Abstract Background Human adipose-derived stem cells (hADSCs) have been used in various fields of tissue engineering because of their promising therapeutic efficacy. However, the stemness of hADSCs cannot be maintained for long durations, and their therapeutic cellular functions, such as paracrine factor secretion decrease during long-term cell culture. To facilitate the use of long-term-cultured hADSCs (L-ADSCs), we designed a novel therapeutic anti-senescence ion-delivering nanocarrier (AIN) that is capable of recovering the therapeutic properties of L-ADSCs. In the present study, we introduced a low-pH-responsive ion nanocarrier capable of delivering transition metal ions that can enhance angiogenic paracrine factor secretion from L-ADSCs. The AINs were delivered to L-ADSCs in an intracellular manner through endocytosis. Results Low pH conditions within the endosomes induced the release of transition metal ions (Fe) into the L-ADSCs that in turn caused a mild elevation in the levels of reactive oxygen species (ROS). This mild elevation in ROS levels induced a downregulation of senescence-related gene expression and an upregulation of stemness-related gene expression. The angiogenic paracrine factor secretion from L-ADSCs was significantly enhanced, and this was evidenced by the observed therapeutic efficacy in response to treatment of a wound-closing mouse model with conditioned medium obtained from AIN-treated L-ADSCs that was similar to that observed in response to treatment with short-term-cultured adipose-derived stem cells. Conclusions This study suggests a novel method and strategy for cell-based tissue regeneration that can overcome the limitations of the low stemness and therapeutic efficacy of stem cells that occurs during long-term cell culture. Graphical Abstract

Pre-conditioning mesenchymal stromal cell spheroids for immunomodulatory paracrine factor secretion

Cytotherapy ◽  
2014 ◽  
Vol 16 (3) ◽  
pp. 331-345 ◽  
Author(s):  
Joshua A. Zimmermann ◽  
Todd C. Mcdevitt
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Paracrine Factor ◽  
Cell Spheroids ◽  
Factor Secretion

Transplantation of Mesenchymal Stem Cells Promotes Tissue Regeneration in a Glaucoma Model Through Laser-Induced Paracrine Factor Secretion and Progenitor Cell Recruitment

Stem Cells ◽  
2013 ◽  
Vol 31 (6) ◽  
pp. 1136-1148 ◽  
Author(s):  
Renaud Manuguerra-GagnÉ ◽  
Patrick R. Boulos ◽  
Ahmed Ammar ◽  
François A. Leblond ◽  
Gorazd Krosl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Progenitor Cell ◽  
Paracrine Factor ◽  
Cell Recruitment ◽  
Factor Secretion

Secretion of a paracrine factor with growth promoting activity for fibroblasts from porcine thyroid follicles

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S45-S46
Author(s):  
W. GREIL ◽  
R. GÄRTNER ◽  
U. RETTENMAIER ◽  
K. HORN ◽  
C. R. PICKARDT
Keyword(s):  
Paracrine Factor ◽  
Growth Promoting

scholarly journals Structure and Regulation of the Salivary Gland Secretion Protein Gene Sgs-1 of Drosophila melanogaster

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 753-762
Author(s):  
Günther E Roth ◽  
Sigrid Wattler ◽  
Hartmut Bornschein ◽  
Michael Lehmann ◽  
Günter Korge
Keyword(s):  
Drosophila Melanogaster ◽  
Tandem Repeats ◽  
Transcriptional Start Site ◽  
Regulatory Elements ◽  
Coding Region ◽  
Band Shift ◽  
Salivary Gland Secretion ◽  
Enhancer Binding Protein ◽  
Factor Secretion ◽  
Third Instar Larvae

Abstract The Drosophila melanogaster gene Sgs-1 belongs to the secretion protein genes, which are coordinately expressed in salivary glands of third instar larvae. Earlier analysis had implied that Sgs-1 is located at the 25B2-3 puff. We cloned Sgs-1 from a YAC covering 25B2-3. Despite using a variety of vectors and Escherichia coli strains, subcloning from the YAC led to deletions within the Sgs-1 coding region. Analysis of clonable and unclonable sequences revealed that Sgs-1 mainly consists of 48-bp tandem repeats encoding a threonine-rich protein. The Sgs-1 inserts from single λ clones are heterogeneous in length, indicating that repeats are eliminated. By analyzing the expression of Sgs-1/lacZ fusions in transgenic flies, cis-regulatory elements of Sgs-1 were mapped to lie within 1 kb upstream of the transcriptional start site. Band shift assays revealed binding sites for the transcription factor fork head (FKH) and the factor secretion enhancer binding protein 3 (SEBP3) at positions that are functionally relevant. FKH and SEBP3 have been shown previously to be involved in the regulation of Sgs-3 and Sgs-4. Comparison of the levels of steady state RNA and of the transcription rates for Sgs-1 and Sgs-1/lacZ reporter genes indicates that Sgs-1 RNA is 100-fold more stable than Sgs-1/lacZ RNA. This has implications for the model of how Sgs transcripts accumulate in late third instar larvae.

Neuregulin-1 Compensates for Endothelial Nitric Oxide Synthase Deficiency

2021 ◽  
Author(s):  
Hadis Shakeri ◽  
Jente R.A. Boen ◽  
Sofie De Moudt ◽  
Jhana O. Hendrickx ◽  
Arthur J.A. Leloup ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Fibrosis ◽  
Separate Experiment ◽  
No Production ◽  
Ang Ii ◽  
Wild Type ◽  
Paracrine Factor ◽  
Renal Hypertrophy ◽  
Neuregulin 1 ◽  
Endothelial Nitric Oxide

Endothelial cells (ECs) secrete different paracrine signals that modulate the function of adjacent cells; two examples of these paracrine signals are nitric oxide (NO) and neuregulin-1 (NRG1), a cardioprotective growth factor. Currently, it is undetermined whether one paracrine factor can compensate for the loss of another. Herein, we hypothesized that NRG1 can compensate for endothelial NO synthase (eNOS) deficiency. Methods. We characterized eNOS null and wild type (WT) mice by cardiac ultrasound and histology and we determined circulating NRG1 levels. In a separate experiment, 8 groups of mice were divided into 4 groups of eNOS null mice and wild type (WT) mice; half of the mice received angiotensin II (Ang II) to induce a more severe phenotype. Mice were randomized to daily injections with NRG1 or vehicle for 28 days. Results. eNOS deficiency increased NRG1 plasma levels, indicating that ECs increase their NRG1 expression when NO production is deleted. eNOS deficiency also increased blood pressure, lowered heart rate, induced cardiac fibrosis, and affected diastolic function. In eNOS null mice, Ang II administration increased cardiac fibrosis, but also induced cardiac hypertrophy and renal fibrosis. NRG1 administration prevented the cardiac and renal hypertrophy and fibrosis caused by Ang II infusion and eNOS deficiency. Moreover, Nrg1 expression in the myocardium is shown to be regulated by miR-134. Conclusion. This study indicates that administration of endothelium-derived NRG1 can compensate for eNOS deficiency in the heart and kidneys.

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