Fibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive muscle degeneration in chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs from healthy and injured muscles across a spectrum of injury. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. We utilize full spectrum flow cytometry to identify distinct FAP subpopulations based on highly multiplexed protein expression. We uncover that injury severity increases adipogenic commitment of FAP subpopulations and is driven by the downregulation of DLK1. Treatment of FAPs with DLK1 reduces adipogenesis, suggesting that during injury, reduced DLK1 within a subpopulation of FAPs may drive adipogenic degeneration. This work highlights how stem cells perform varied functions depending on tissue context, by dynamically regulating subpopulation fate commitment, which can be targeted improve patient outcomes after injury.

Acute promyelocytic leukemia (APL) during pregnancy is rare and difficult to treat. To the best of our knowledge, there is little precedent for successful treatment with combined chemotherapeutic agents without affecting delivery. The present study reported the case of a 31-year-old woman pregnant with twins who presented to the antenatal service at 13-week gestational age with complaints of vaginal bleeding, lower abdominal pain, bleeding gums and skin ecchymosis, and was eventually diagnosed with APL. After treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction regimen, the patient achieved a complete remission (CR) and delivered two healthy male infants at 34 weeks of gestation. The use of ATRA and ATO for the treatment of APL is controversial due to teratogenic effects and lethal retinoic acid syndrome. However, the patient demonstrated that the chemotherapy regimen with ATRA and ATO during the second and third trimesters can result in a sustainable remission and successful pregnancy outcome.
Copyright © 2020, Spandidos Publications.

Low-intensity ultrasound (LIUS) enhances the proliferation rate of various mammalian stem cells through mechanical stimulation. This study quantitively finds suitable LIUS stimulation parameters for increasing the proliferation rate of human adipose-derived mesenchymal stem cells (hAdMSCs) for mass production. Various stimulation conditions of LIUS were assessed based on the beam pattern of the ultrasonic transducer and the attenuation of the sound waves. Using optimal LIUS stimulation parameters for enhancing proliferation of hAdMSCs taken from bromodeoxyuridine (BrdU) incorporation assay, long-term culture of hAdMSCs was performed for 16 days. The resultant hAdMSCs were characterized for various biomarkers such as CD34-, CD45-, CD73+, CD95+, CD105+ and cytological staining and a cytokine array assay. LIUS stimulation parameters found for enhancing the hAdMSCs proliferation were the frequency of 5 MHz, an intensity of 300 mWcm-2, a duration of 10 min per day, and continuous waves with a 100% duty cycle. The LIUS stimulated hAdMSCs group showed a 3.25-fold increase in the cell number compared to the control group after 16 days of culture. By confirming the effects of quantitatively measured LIUS stimulation on the enhancement of hAdMSCs proliferation, this study may be a foundation for the applications of LIUS stimulation in the industrial-scale production of hAdMSCs.
© 2022. The Author(s).

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n = 232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n = 37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether the independence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and ethnicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n=232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n=37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether in-dependence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and eth-nicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.