Following full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound “closure” in patients is autologous split-thickness skin grafting ...(STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.
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•Dermal progenitor cells can be isolated and expanded in vitro from adult human skin•DPC transplant beneath skin grafts improves mechanical function and limits pruritus•Inclusion of scaffolds improves cell engraftment but impedes graft take and function•DPCs support improved skin graft function relative to cultured dermal fibroblasts
The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem cells and neighboring mesenchyme. Recent work described the existence of HF dermal stem cells ...(hfDSCs), but the genetic regulation of hfDSCs and their daughter cell lineages in HF regeneration remains unknown. Here we prospectively isolate functionally distinct mesenchymal compartment in the HF (dermal cup DC; includes hfDSCs and dermal papilla) and define the transcriptional programs involved in hfDSC function and acquisition of divergent mesenchymal fates. From this, we demonstrate cross-compartment mesenchymal signaling within the HF niche, whereby DP-derived R-spondins act to stimulate proliferation of both hfDSCs and epithelial progenitors during HF regeneration. Our findings describe unique transcriptional programs that underlie the functional heterogeneity among specialized fibroblasts within the adult HF and identify a novel regulator of mesenchymal progenitor function during tissue regeneration.
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•Transcriptional compartmentalization of the hair follicle mesenchyme•Hair follicle dermal stem cells (hfDSCs) exhibit a unique gene expression profile•DP-derived R-spondins coordinately activate hfDSCs and epithelial progenitors•Gene expression profiling of hair follicle dermal stem cells
Biological Sciences; Developmental Biology; Stem Cells Research
Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self‐renewing colonies called skin‐derived precursors (SKPs). Following ...transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred‐suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor‐expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. Stem Cells Translational Medicine 2017;6:434–443
Cell-based therapies have garnered considerable interest largely because of their potential utility for tissue regeneration in a variety of organs, including skin. Designing vehicles that enable ...optimal delivery and purposeful integration of donor cells within tissues will be critical for their success. Here, we investigate the utility of an injectable, self-polymerizing, fully synthetic hydrogel in supporting the survival, proliferation, and function of cultured adult dermal progenitor cells (DPCs) which may serve as a source of renewable cells to repair severe skin injuries or restore hair growth. We show that modifying the stiffness of these transglutaminase cross-linked poly(ethylene glycol) (TG-PEG) hydrogels significantly alters DPC behavior and phenotype; increasing stiffness promotes their differentiation and migration whereas softer gels maintained them in a proliferative state. We found that 2–3% TG-PEG was optimal to promote cell expansion and survival. Unexpectedly, DPCs grown in all conditions maintained their inductive function and thus generated de novo hair follicles. Our data suggests that TG-PEG hydrogels may be a versatile platform for stem and progenitor cell transplantation and fate specification while maintaining functional competence.
ABSTRACT
Objective
To report complications of arthrodesis of the carpometacarpal (CMC) joint using a drilling technique in an adult horse.
Study Design
Case report.
Animals
Horse (n = 1).
Method
A ...12‐year‐old Quarter Horse mare with CMC osteoarthritis (CMC‐OA) had arthrodesis under general anesthesia in right lateral recumbency. Under fluoroscopic guidance, a 4.5 mm drill bit was inserted at 3 drilling sites 5–6 cm into the CMC joint and was fanned 30–45° in the plane of the joint and 5–10° in the long axis of the limb to destroy articular cartilage and expose the subchondral bone.
Results
The horse presented 2 weeks after surgery for severe lameness of the operated limb. A slab fracture of the 2nd carpal bone (C2) and subluxation of the middle carpal (MC) joint was diagnosed. The horse was humanely euthanatized due to poor prognosis.
Conclusion
The fanning technique of arthrodesis of the CMC joint may lead to fracture of carpal bones, joint instability, and MC joint subluxation. A balance between articular surface destruction and maintenance of joint stability should be achieved when using this technique.
A cow, presented after being struck by a motor vehicle, continued to have difficulty eating after mandibular fracture repair. Imaging showed a temporomandibular luxation and a mandibular condylectomy ...was performed. Mastication improved greatly but the cow was euthanized due to infection. This is the first report of mandibular condylectomy in cattle.
Case Description--3 horses were referred for treatment of subchondral cystic lesions of 1 or both medial femoral condyles. Clinical Findings--All horses had clinically apparent lameness confirmed to ...be due to a radiographically evident subchondral cystic lesion of the medial femoral condyle with a large articular component (> 15 mm) and shallow subchondral depth (< 10 mm). Arthroscopic assessment of affected cartilage revealed undulating cartilage with a relatively smooth surface and extensive residual perimeter attachment. Treatment and Outcome--Resorbable polydioxanone pins were used arthroscopically to reattach the cartilage overlying the subchondral cystic lesions. A biologic graft (bone marrow aspirate concentrate or allogeneic chondrocytes) was injected into the depths of the cystic cavity following cartilage reattachment. Follow-up examination confirmed radiographic resolution of the lesion and elimination of clinical signs within the treated femorotibial joint. Clinical Relevance--Lesions with a large area of affected articular cartilage have been associated with a decreased rate of return to athletic function following arthroscopic debridement, likely secondary to the loss of subchondral architecture and the production of imperfect fibrocartilage repair. Salvage of the affected cartilage in a select population of horses with progressively expanding but shallow subchondral cystic lesions of the medial femoral condyle is possible and may improve radiographic and clinical outcome.
To determine the incidence of postoperative ileus (POI) in a population of horses after small intestinal surgery and the effect of multiple variables on development of POI. Case series. Horses ...(n=233) aged greater-than-or-equal1 year that had exploratory celiotomy for small intestinal disease that recovered from surgery from 1995 to 2005. Sixty-eight variables were collected from medical records (1995-2005) for each horse. POI was defined as nasogastric reflux volume >20 L over 24 hours or >8 L at any single time after surgery. Twenty-seven percent (64/233) of horses developed POI; 29 of 64 (46%) horses with POI had duodenitis proximal jejunitis (DPJ). When no intestinal resection was required at surgery, excluding horses with DPJ, 15% of horses had POI; 30% horses had POI after intestinal resection. Ten percent of horses had POI for >24 hours. When horses with DPJ were excluded, factors associated with increased risk of POI included high packed cell volume at hospital admission (P=.024), increasing age (P=.0004), and length of intestinal resection (P=.05). Risk factors for POI in this study were nonspecific although horses with intestinal resection are at higher risk compared with horses without intestinal resection. Predicting with certainty which cases will develop POI remains elusive.
Objective: To determine in vitro elution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP).
Sample Population: Experimental.
Methods: FRCP beads with ...water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate‐buffered saline (PBS) at 37°C, 5% CO2 and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were determined.
Results: Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC0–∞) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t=1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D).
Conclusions: FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation.
Clinical Relevance: Duration before complete resorption of FRCP beads in vivo should be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.
3 foals were referred for treatment of tympany of the auditory tube diverticulum (guttural pouch).
Bilateral guttural pouch tympany was diagnosed in all 3 foals on the basis of clinical signs and ...results of radiographic and endoscopic evaluations and gutturocentesis. In each foal, previous medical or surgical interventions or both had failed to correct the problem.
Bilateral surgical resection of the plica salpingopharyngeus was performed. Follow-up telephone interviews with owners 8 months to 3 years after surgery revealed that long-term resolution of the tympany had been achieved in each foal, with few to no postsurgical complications.
Surgical correction of refractory bilateral guttural pouch tympany can be accomplished by resection of the plica salpingopharyngeus within the pharyngeal opening of the Eustachian tube. In the foals of this report, permanent resolution of tympany was apparently achieved without interfering with upper airway function, providing support for the use of surgical resection of the plica salpingopharyngeus in the treatment of bilateral guttural pouch tympany.
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