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Article: Isolation and Characterisation of an Adipose-derived human mesenchymal stem cell line - '

Visweswaran, Malini / Cunningham, Corey William / Sidhu, Kuldip Singh

Journal of stem cells & regenerative medicine

2022 Volume 18, Issue 1, Page(s) 2–10

Abstract: Mesenchymal stem cells derived from adipose tissue (ADMSCs) are being increasingly considered in regenerative medicine-based clinical applications. Apart from possessing therapeutic applications themselves, ADMSCs also secrete a myriad of soluble factors ...

Abstract	Mesenchymal stem cells derived from adipose tissue (ADMSCs) are being increasingly considered in regenerative medicine-based clinical applications. Apart from possessing therapeutic applications themselves, ADMSCs also secrete a myriad of soluble factors which are promising candidates for treating several degenerative diseases such as osteoarthritis and neurodegenerative diseases, wound repair as well as for cosmeceutical purposes. In our research study, we successfully isolated ADMSCs in-house, now called CKC-Endeavour-1 from the lipoaspirate sample of a patient who underwent liposuction. The subsequent expansion of cells was performed in xeno-free and serum-free conditions and their characterisation was performed using tri-lineage differentiation studies. The levels of differentiation were assessed by staining and gene expression which was observed to be comparable between the in-house developed ADMSC cell line and the commercially purchased ADMSCs. Following characterisation, the secretory components from these MSCs, namely, conditioned media (ADMSC-CM) and exosomes (ADMSC-EXO) were harvested from CKC-Endeavour-1 under xeno-free, serum-free, and supplement-free conditions followed by lyophilisation in order to attempt to prolong its shelf-life. The comprehensive analysis of the secretome profile of ADMSC-CM using carried out using cytokine array and demonstrated the presence of 105 cytokines and growth factors. Also, clinical grade Izon columns were used to isolate the exosomes from ADMSC-CM obtaining exosomes in the size range of <200nm, analysed using nanoparticle tracking analysis. Overall, our study developed an ADMSC cell line, CKC-Endeavour-1, along with their CM and exosome (EXO) products under clinically safe conditions. Additionally, we have obtained a comprehensive understanding of the secreted factors present in the ADMSC-CM which could be further explored in detail to tap the best therapeutic benefits from them.
Language	English
Publishing date	2022-04-05
Publishing country	India
Document type	Journal Article
ZDB-ID	2587301-5
ISSN	0973-7154
ISSN	0973-7154
DOI	10.46582/jsrm.1801002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport.

Cunningham, Corey N / Rutter, Jared

EMBO reports

2020 Volume 21, Issue 5, Page(s) e50071

Abstract: The metabolic compartmentalization enabled by mitochondria is key feature of many cellular processes such as energy conversion to ATP production, redox balance, and the biosynthesis of heme, urea, nucleotides, lipids, and others. For a majority of these ... ...

Abstract	The metabolic compartmentalization enabled by mitochondria is key feature of many cellular processes such as energy conversion to ATP production, redox balance, and the biosynthesis of heme, urea, nucleotides, lipids, and others. For a majority of these functions, metabolites need to be transported across the impermeable inner mitochondrial membrane by dedicated carrier proteins. Here, we examine the substrates, structural features, and human health implications of four mitochondrial metabolite carrier families: the SLC25A family, the mitochondrial ABCB transporters, the mitochondrial pyruvate carrier (MPC), and the sideroflexin proteins.
MeSH term(s)	Biological Transport ; Carrier Proteins/metabolism ; Humans ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/genetics ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Membranes/metabolism
Chemical Substances	Carrier Proteins ; Mitochondrial Membrane Transport Proteins
Language	English
Publishing date	2020-04-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202050071
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Article ; Online: Mesenchymal stem cell-secretome laden photopolymerizable hydrogels for wound healing.

Doshi, Riddhesh B / Vakil, Devashree / Molley, Thomas G / Islam, Md Shariful / Kilian, Kristopher A / Cunningham, Corey / Sidhu, Kuldip S

Journal of biomedical materials research. Part A

2024

Abstract: Mesenchymal stem cell-derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti-inflammatory, immunomodulatory, and wound healing properties. However, maintaining ... ...

Abstract	Mesenchymal stem cell-derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti-inflammatory, immunomodulatory, and wound healing properties. However, maintaining therapeutic efficacy and ensuring stability of cell-based products is challenging, requiring a robust delivery method. Therefore, we designed a hydrogel-based scaffold loaded with CK Cell Technologies' proprietary Mesenchymal stem cell-secretome for controlled release treatment of acute and chronic wounds. We incorporated both conditioned media (CM) and extracellular vesicles (EVs) into gelatin methacryloyl (GelMA) hydrogels and demonstrated how we can tune the diffusive release of the EVs from them. To demonstrate viability of the approach, we developed a wound healing scratch assay where we see in situ release of CM and EVs promote enhanced migration of human dermal fibroblasts (hDFs). We see the colocalization of these EVs in the fibroblasts using fluorescent microscopy. Finally, as a surrogate for in vivo neovascularization, we conducted an in vitro tube formation assay for the MSC-secretome using matrigel-embedded human microvascular endothelial cells. By adding CM and EVs, we observe an increase in tubulogenesis. Collectively, our data demonstrates by tuning the GelMA properties, we can influence the controlled release of the MSC-secretome for a wound dressing and bandage application for chronic and acute wounds.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37697
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Article ; Online: Benefits of Using an Appropriately Formulated Wipe to Clean Diapered Skin of Preterm Infants.

Vongsa, Rebecca / Rodriguez, Karien / Koenig, David / Cunningham, Corey

Global pediatric health

2019 Volume 6, Page(s) 2333794X19829186

Abstract: The skin of premature infants is underdeveloped rendering it more prone to break down and irritation. Therefore, special care is needed to protect premature skin and ensure it is not adversely affected. Many health care professionals advise using just ... ...

Abstract	The skin of premature infants is underdeveloped rendering it more prone to break down and irritation. Therefore, special care is needed to protect premature skin and ensure it is not adversely affected. Many health care professionals advise using just water and cloth to clean diapered skin after a bowel movement despite evidence that shows improved infant skin health with the use of modern appropriately formulated baby wipes. This article describes the unique physiology of premature infant skin, reviews clinical evidence comparing use of baby wipes to water and cloth, and describes attributes of appropriately formulated baby wipes.
Language	English
Publishing date	2019-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2785531-4
ISSN	2333-794X ; 2333-794X
ISSN (online)	2333-794X
ISSN	2333-794X
DOI	10.1177/2333794X19829186
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Article: Do rugby league players under-report concussion symptoms? A cross-sectional study of elite teams based in Australia.

Longworth, Thomas / McDonald, Andrew / Cunningham, Corey / Khan, Hussain / Fitzpatrick, Jane

BMJ open sport & exercise medicine

2021 Volume 7, Issue 1, Page(s) e000860

Abstract: Objective: To determine the rate of under-reporting of concussion and its symptoms in elite rugby league players in Australia.: Methods: The study was conducted in the preseason of the 2020 National Rugby League (NRL) competition.A total of 151 male, ...

Abstract	Objective: To determine the rate of under-reporting of concussion and its symptoms in elite rugby league players in Australia. Methods: The study was conducted in the preseason of the 2020 National Rugby League (NRL) competition.A total of 151 male, NRL club contracted rugby league players across three professional clubs participated.The participants completed a voluntary, anonymous survey exploring player demographics, concussion data, under-reporting instances and reasons for under-reporting over the 2018 and 2019 rugby league seasons. Results: 17.2% of surveyed players reported sustaining a likely concussion over the past 2 years and not reporting to medical staff. 22% of NRL first grade players admitted to not reporting at least one concussion during the 2018 and 2019 seasons. The most common reason Conclusions: 17.2 % of elite rugby league players in Australia chose not to report likely concussive episodes and concussion-related symptoms during the 2018 and 2019 seasons. Clinicians need to be aware of under-reporting in athletes when assessing players following head injuries. The findings highlight the need for development of validated, objective testing for concussion following sports-associated head injury.
Language	English
Publishing date	2021-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2817580-3
ISSN	2055-7647
ISSN	2055-7647
DOI	10.1136/bmjsem-2020-000860
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Article ; Online: The science behind wet wipes for infant skin: Ingredient review, safety, and efficacy.

Rodriguez, Karien J / Cunningham, Corey / Foxenberg, Robert / Hoffman, Douglas / Vongsa, Rebecca

Pediatric dermatology

2020 Volume 37, Issue 3, Page(s) 447–454

Abstract: In the diapered area, the continuous exposure to excess moisture and irritants from urine and feces weakens the stratum corneum, making the skin more susceptible to irritation. The use of wet wipes for infants (baby wipes) is a common practice to clean ... ...

Abstract	In the diapered area, the continuous exposure to excess moisture and irritants from urine and feces weakens the stratum corneum, making the skin more susceptible to irritation. The use of wet wipes for infants (baby wipes) is a common practice to clean skin after urine or a bowel movement, and this practice even extends to cleaning the hands and face, resulting in repeated daily use. Therefore, ensuring that baby wipes contain ingredients that are safe and mild on skin is important to help minimize skin irritation and discomfort. While disposable baby wipes have been shown to be effective and gentle at cleaning infant skin, even the skin of premature infants, there is growing public concern regarding their safety and tolerability. Not all products are made the same, as differences exist in manufacturing processes, ingredients, materials, safety, and quality testing. Therefore, it is important that healthcare professionals have accessible evidenced-based information on the safety and tolerability of common ingredients found in baby wipes to optimally educate their patients and families. Herein, we provide a review on best practices for ingredient selection, safety, and efficacy of baby wipes.
MeSH term(s)	Child ; Epidermis ; Humans ; Infant ; Infant Care ; Skin ; Skin Care
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605539-4
ISSN	1525-1470 ; 0736-8046
ISSN (online)	1525-1470
ISSN	0736-8046
DOI	10.1111/pde.14112
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Article: Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates

Cunningham, Corey N / Williams, Jeffrey M / Knupp, Jeffrey / Arunagiri, Anoop / Arvan, Peter / Tsai, Billy

Molecular cell. 2019 Aug. 08, v. 75, no. 3

2019

Abstract: Insulin gene coding sequence mutations are known to cause mutant INS-gene-induced diabetes of youth (MIDY), yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely understood. Here, we report that Akita mutant ... ...

Abstract	Insulin gene coding sequence mutations are known to cause mutant INS-gene-induced diabetes of youth (MIDY), yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely understood. Here, we report that Akita mutant proinsulin forms detergent-insoluble aggregates that entrap wild-type (WT) proinsulin in the endoplasmic reticulum (ER), thereby blocking insulin production. Two distinct quality-control mechanisms operate together to combat this insult: the ER luminal chaperone Grp170 prevents proinsulin aggregation, while the ER membrane morphogenic protein reticulon-3 (RTN3) disposes of aggregates via ER-coupled autophagy (ER-phagy). We show that enhanced RTN-dependent clearance of aggregated Akita proinsulin helps to restore ER export of WT proinsulin, which can promote WT insulin production, potentially alleviating MIDY. We also find that RTN3 participates in the clearance of other mutant prohormone aggregates. Together, these results identify a series of substrates of RTN3-mediated ER-phagy, highlighting RTN3 in the disposal of pathogenic prohormone aggregates.
Keywords	autophagy ; diabetes ; endoplasmic reticulum ; genes ; mutants ; mutation ; proinsulin ; quality control ; youth
Language	English
Dates of publication	2019-0808
Size	p. 442-456.e4.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.05.011
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Article ; Online: From da Vinci to definitive diagnosis: how training in sports ultrasound harnesses sound, science and skill.

Patricios, Jon / Rossiter, Michael / Cunningham, Corey / Fitzpatrick, Jane / Hirschmueller, Anja / Mweli, Thamsanqa / Roos, Beverly / Thornton, Jane S

British journal of sports medicine

2021 Volume 56, Issue 3, Page(s) 118–119

MeSH term(s)	Clinical Competence ; Humans ; Ultrasonography
Language	English
Publishing date	2021-06-30
Publishing country	England
Document type	Editorial
ZDB-ID	600592-5
ISSN	1473-0480 ; 0306-3674
ISSN (online)	1473-0480
ISSN	0306-3674
DOI	10.1136/bjsports-2021-104667
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Article ; Online: Phosphate starvation signaling increases mitochondrial membrane potential through respiration-independent mechanisms.

eLife

2024 Volume 13

Abstract: Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells ... ...

Abstract	Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of mitochondrial health. Given its central importance, it is logical that cells would modulate mitochondrial membrane potential in response to demand and environmental cues, but there has been little exploration of this question. We report that loss of the Sit4 protein phosphatase in yeast increases mitochondrial membrane potential, both by inducing the electron transport chain and the phosphate starvation response. Indeed, a similarly elevated mitochondrial membrane potential is also elicited simply by phosphate starvation or by abrogation of the Pho85-dependent phosphate sensing pathway. This enhanced membrane potential is primarily driven by an unexpected activity of the ADP/ATP carrier. We also demonstrate that this connection between phosphate limitation and enhancement of mitochondrial membrane potential is observed in primary and immortalized mammalian cells as well as in
MeSH term(s)	Animals ; Membrane Potential, Mitochondrial ; Phosphates/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Adenosine Triphosphate/metabolism ; Respiration ; Mammals/metabolism
Chemical Substances	Phosphates ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2024-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.84282
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Article ; Online: Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates.

Cunningham, Corey N / Williams, Jeffrey M / Knupp, Jeffrey / Arunagiri, Anoop / Arvan, Peter / Tsai, Billy

Molecular cell

2019 Volume 75, Issue 3, Page(s) 442–456.e4

Abstract	Insulin gene coding sequence mutations are known to cause mutant INS-gene-induced diabetes of youth (MIDY), yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely understood. Here, we report that Akita mutant proinsulin forms detergent-insoluble aggregates that entrap wild-type (WT) proinsulin in the endoplasmic reticulum (ER), thereby blocking insulin production. Two distinct quality-control mechanisms operate together to combat this insult: the ER luminal chaperone Grp170 prevents proinsulin aggregation, while the ER membrane morphogenic protein reticulon-3 (RTN3) disposes of aggregates via ER-coupled autophagy (ER-phagy). We show that enhanced RTN-dependent clearance of aggregated Akita proinsulin helps to restore ER export of WT proinsulin, which can promote WT insulin production, potentially alleviating MIDY. We also find that RTN3 participates in the clearance of other mutant prohormone aggregates. Together, these results identify a series of substrates of RTN3-mediated ER-phagy, highlighting RTN3 in the disposal of pathogenic prohormone aggregates.
MeSH term(s)	Autophagy/genetics ; Carrier Proteins/genetics ; Diabetes Mellitus/genetics ; Diabetes Mellitus/pathology ; Endoplasmic Reticulum/genetics ; HEK293 Cells ; HSP70 Heat-Shock Proteins/genetics ; Humans ; Insulin/biosynthesis ; Insulin/genetics ; Membrane Proteins/genetics ; Mutation/genetics ; Nerve Tissue Proteins/genetics ; Proinsulin/biosynthesis ; Proinsulin/genetics ; Protein Aggregates/genetics ; Protein Folding ; RNA, Small Interfering/genetics
Chemical Substances	Carrier Proteins ; HSP70 Heat-Shock Proteins ; Insulin ; Membrane Proteins ; Nerve Tissue Proteins ; Protein Aggregates ; RNA, Small Interfering ; RTN3 protein, human ; oxygen-regulated proteins ; Proinsulin (9035-68-1)
Language	English
Publishing date	2019-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.05.011
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