scholarly journals Periodic thermomechanical modulation of toll-like receptor expression and distribution in mesenchymal stromal cells

Author(s):  
Xun Xu ◽  
Yan Nie ◽  
Weiwei Wang ◽  
Nan Ma ◽  
Andreas Lendlein

Abstract Toll-like receptor (TLR) can trigger an immune response against virus including SARS-CoV-2. TLR expression/distribution is varying in mesenchymal stromal cells (MSCs) depending on their culture environments. Here, to explore the effect of periodic thermomechanical cues on TLRs, thermally controlled shape-memory polymer sheets with programmable actuation capacity were created. The proportion of MSCs expressing SARS-CoV-2-associated TLRs was increased upon stimulation. The TLR4/7 colocalization was promoted and retained in the endoplasmic reticula. The TLR redistribution was driven by myosin-mediated F-actin assembly. These results highlight the potential of boosting the immunity for combating COVID-19 via thermomechanical preconditioning of MSCs. Graphic abstract Periodic thermal and synchronous mechanical stimuli provided by polymer sheet actuators selectively promoted the expression of SARS-CoV-2-associated TLRs 4 and 7 in adipose-derived MSCs and recruited TLR4 to Endoplasmic reticulum region where TLR7 was located via controlling myosin-mediated F-actin cytoskeleton assembly.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Maurice A. Canham ◽  
John D. M. Campbell ◽  
Joanne C. Mountford

Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.


2019 ◽  
Vol 234 (11) ◽  
pp. 21145-21152 ◽  
Author(s):  
Mehdi Najar ◽  
Catherine A. Lombard ◽  
Hussein Fayyad‐Kazan ◽  
Wissam H. Faour ◽  
Makram Merimi ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-2
Author(s):  
Fabiana Evaristo-Mendonça ◽  
Gabriela Sardella-Silva ◽  
Tais Hanae Kasai-Brunswick ◽  
Raquel Maria Pereira Campos ◽  
Pablo Domizi ◽  
...  

2018 ◽  
Vol 27 (8) ◽  
pp. 1210-1221 ◽  
Author(s):  
A. Liew ◽  
C. Baustian ◽  
D. Thomas ◽  
E. Vaughan ◽  
C. Sanz-Nogués ◽  
...  

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.


2019 ◽  
Vol 203 (10) ◽  
pp. 2735-2745 ◽  
Author(s):  
Gaël Moquin-Beaudry ◽  
Chloé Colas ◽  
Yuanyi Li ◽  
Renée Bazin ◽  
Jean V. Guimond ◽  
...  

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