Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells.

Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

Proceedings of the United Kingdom Periprosthetic Joint Infection Meeting 2022: Combined and Arthroplasty Sessions.

Considerable variation in practice exists in the prevention, diagnosis, and treatment of periprosthetic joint infection (PJI), which is a devastating complication for patients and surgeons. The consensus principle has been increasingly embraced by the orthopaedic community to help guide practice, especially where high-level evidence remains unavailable. The third United Kingdom Periprosthetic Joint Infection (UK PJI) Meeting was held in Glasgow on April 1, 2022, with more than 180 delegates in attendance, representing orthopaedics, microbiology, infectious diseases, plastic surgery, anesthetics, and allied health professions, including pharmacy and arthroplasty nurses. The meeting comprised a combined session for all delegates, and separate breakout sessions for arthroplasty and fracture-related infection. Consensus questions for each session were prepared in advance by the UK PJI working group, based upon topics that were proposed at previous UK PJI Meetings, and delegates participated in an anonymized electronic voting process. We present the findings of the combined and arthroplasty sessions of the meeting in this article, and each consensus topic is discussed in relation to the contemporary literature.