Stem cell therapy has emerged as a promising regenerative medicine strategy but is limited by poor cell survival, leading to low therapeutic outcomes. We developed cell spheroid therapeutics to overcome this limitation. We utilized solid-phase FGF2 to form functionally enhanced cell spheroid-adipose derived (FECS-Ad), a type of cell spheroid that preconditions cells with intrinsic hypoxia to increase the survival of transplanted cells. We demonstrated an increase in hypoxia-inducible factor 1-alpha (HIF-1α) levels in FECS-Ad, which led to the upregulation of tissue inhibitor of metalloproteinase 1 (TIMP1). TIMP1 enhanced the survival of FECS-Ad, presumably through the CD63/FAK/Akt/Bcl2 anti-apoptotic signaling pathway. Cell viability of transplanted FECS-Ad was reduced by TIMP1 knockdown in an in vitro collagen gel block and a mouse model of critical limb ischemia (CLI). TIMP1 knockdown in FECS-Ad inhibited angiogenesis and muscle regeneration induced by FECS-Ad transplanted into ischemic mouse tissue. Genetic overexpression of TIMP1 in FECS-Ad further promoted the survival and therapeutic efficacy of transplanted FECS-Ad. Collectively, we suggest that TIMP1 acts as a key survival factor to improve the survival of transplanted stem cell spheroids, which provides scientific evidence for enhanced therapeutic efficacy of stem cell spheroids, and FECS-Ad as a potential therapeutic agent to treat CLI. STATEMENT OF SIGNIFICANCE: We used FGF2-tethered substrate platform to form adipose-derived stem cell spheroids, as we named as functionally enhanced cell spheroid-adipose derived (FECS-Ad). In this paper, we showed that intrinsic hypoxia of spheroids upregulated expression of HIF-1α, which in turn upregulated expression of TIMP1. Our paper highlights TIMP1 as a key survival factor to improve survival of transplanted stem cell spheroids. We believe that our study has a very strong scientific impact as extending transplantation efficiency is essential for successful stem cell therapy.

01 Nov 2021·Journal of Clinical Sleep MedicineQ3 · MEDICINE

The influence of antidepressants and actigraphy-derived sleep characteristics on pediatric multiple sleep latency testing

Q3 · MEDICINE

Article

Author: Kotagal, Suresh ; Dhankikar, Swati ; Kolla, Bhanu Prakash ; Mansukhani, Meghna P.

STUDY OBJECTIVESResearch evaluating the influence of rapid eye movement suppressing antidepressants (REMS-AD) on multiple sleep latency test (MSLT) results and the value of performing actigraphy prior to this test in children and adolescents is lacking. We examined the impact of REMS-AD and actigraphy parameters on mean sleep latency (MSL) and sleep-onset REM episodes (SOREMs) on MSLT in a pediatric clinical sample.METHODSThis was a retrospective chart review at a quarternary referral center. We identified 164 MSLTs conducted in patients aged less than 18 years between 2014 and 2017. Correlations between REMS-AD, self-reported sleep duration, actigraphy parameters, and each of the outcomes (MSL and SOREMs) were examined. Regression analyses accounting for clinical characteristics were performed.RESULTSMean age of the sample was 11.9 ± 4.19 years, 62% were female, 28 (17%) were on REMS-AD (48% of whom were able to discontinue these medications prior to MSLT), and mean pediatric daytime sleepiness score was 21.7 ± 6.1. MSL was 11.27 ± 5.77 min and mean number of SOREMs 0.55 ± 1.04. Patients on a REMS-AD at initial assessment had fewer SOREMs compared to those not taking these medications (0.17 ± 0.19 vs 0.62 ± 0.09; P = .04); no difference was noted in MSL (10.36 ± 1.10 vs 11.47 ± 0.50; P = .36). Increased time in bed on actigraphy correlated with a longer MSL and fewer SOREMs (r = .23; P = .04 and r = .316; P = .004, respectively). Following regression analyses, use of REMS-AD continued to remain associated with fewer SOREMs; greater time in bed on actigraphy, but not self-reported sleep duration, was associated with a longer MSL (all P < .05).CONCLUSIONSClinicians should account for the use of REMS-AD and utilize actigraphy to determine time in bed while interpreting the results of a pediatric MSLT.CITATIONMansukhani MP, Dhankikar S, Kotagal S, Kolla BP. The influence of antidepressants and actigraphy-derived sleep characteristics on pediatric multiple sleep latency testing. J Clin Sleep Med. 2021;17(11):2179-2185.

15 Nov 2020·Journal of Clinical Sleep MedicineQ3 · MEDICINE

Advance taper of antidepressants prior to multiple sleep latency testing increases the number of sleep-onset rapid eye movement periods and reduces mean sleep latency

Q3 · MEDICINE

Article

Author: Silber, Michael H. ; Kolla, Bhanu Prakash ; Mansukhani, Meghna P. ; Dhankikar, Swati ; Samman, Hala ; Jahani Kondori, Marjan

STUDY OBJECTIVESPatients presenting with excessive sleepiness are frequently using antidepressant medication(s). While practice parameters recommend discontinuation of antidepressants prior to multiple sleep latency testing (MSLT), data examining the impact of tapering these medications on MSLT results are limited.METHODSAdult patients who underwent MSLT at Mayo Clinic Rochester, Minnesota, between 2014 and 2018 were included. Clinical and demographic characteristics, medications, including use of rapid eye movement-suppressing antidepressants (REMS-ADs) at assessment and during testing, actigraphy, and polysomnography data were manually abstracted. The difference in number of sleep-onset rapid eye movement periods (SOREMs), proportion with ≥2 SOREMs, and mean sleep latency in patients who were using REMS-ADs and discontinued prior to testing versus those who remained on REMS-ADs were examined. At our center, all antidepressants are discontinued 2 weeks prior to MSLT, wherever feasible; fluoxetine is stopped 6 weeks prior. Regression analyses accounting for demographic, clinical, and other medication-related confounders were performed.RESULTSA total of 502 patients (age = 38.18 ± 15.90 years; 67% female) underwent MSLT; 178 (35%) were taking REMS-ADs at the time of assessment. REMS-AD was discontinued prior to MSLT in 121/178 (70%) patients. Patients whose REMS-AD was discontinued prior to MSLT were more likely to have ≥2 SOREMs (odds ratio: 12.20; 95% confidence interval: 1.60-92.94) compared with patients on REMS-ADs at MSLT. They also had shorter mean sleep latency (8.77 ± 0.46 vs 10.21 ± 0.28 minutes; P > .009) and higher odds of having ≥2 SOREMs (odds ratio: 2.22; 95% confidence interval: 1.23-3.98) compared with patients not taking REMS-ADs at initial assessment. These differences persisted after regression analyses accounting for confounders.CONCLUSIONSPatients who taper off REMS-ADs prior to MSLT are more likely to demonstrate ≥2 SOREMs and have a shorter mean sleep latency. Pending further prospective investigations, clinicians should preferably withdraw REMS-ADs before MSLT. If this is not done, the test interpretation should include a statement regarding the potential effect of the drugs on the results.

100 Deals associated with FECS-Ad

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic Limb-Threatening Ischemia	Phase 2	KR	S.Biomedics Co., Ltd.	16 Aug 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

FECS-Ad

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation