Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

Background And Objectives: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI.

Methods: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted.

Determining the Minimally Clinically Important Difference for the Disability Rating Scale in Persons With Chronic Traumatic Brain Injury.

The Extended Glasgow Outcome Scale (GOSE) is accepted as the primary outcome measure in registrational studies for traumatic brain injury (TBI). The Disability Rating Scale (DRS) is used to assess functional progress from initial acute injury, through rehabilitation and reintegration into the community and life. For these reasons, the DRS is an alternative measure for assessing meaningful global outcomes in chronic TBI.

Determining minimally clinically important differences for outcome measures in patients with chronic motor deficits secondary to traumatic brain injury.

Objective: To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI).

Methods: Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates.

Clinical Relevance of Elastin in the Structure and Function of Skin.

Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors.

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

Objective: To determine whether chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).

Methods: This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 Stem Cell Therapy for Traumatic Brain Injury (STEMTRA) trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multicenter trial (n = 63) underwent randomization in a 1:1:1:1 ratio to 2.

Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study.

Objective: The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.

Methods: This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.

Deficiency of the Wnt receptor Ryk causes multiple cardiac and outflow tract defects.

Ryk is a member of the receptor tyrosine kinase (RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinase activity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice.

αSMA Expression in Large Colonies of Colony-Forming Units-Fibroblast as an Early Predictor of Bone Marrow MSC Expandability.

Clinical applications of mesenchymal stromal cells (MSCs) require the manufacture of large cell lots, which involves multiple passages for cell expansion and sometimes genetic modification. MSCs from various sources, including bone marrow (BM), exhibit high donor-to-donor variability in their growth characteristics. This can lead to unpredictable manufacturing outcomes with respect to success or failure of individual lots.

Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study.

Background And Purpose: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes.

Methods: Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow-derived mesenchymal stem cells (SB623).

Results: All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event.

Cell Injury-Induced Release of Fibroblast Growth Factor 2: Relevance to Intracerebral Mesenchymal Stromal Cell Transplantations.

Beneficial effects of intracerebral transplantation of mesenchymal stromal cells (MSC) and their derivatives are believed to be mediated mostly by factors produced by engrafted cells. However, the mesenchymal cell engraftment rate is low, and the majority of grafted cells disappear within a short post-transplantation period. Here, we hypothesize that dying transplanted cells can affect surrounding tissues by releasing their active intracellular components.

Cell-based regenerative approaches to the treatment of oral soft tissue defects.

Oral soft tissue plays an important role in the structure and function of the oral cavity by protecting against exogenous substances, pathogens, and mechanical stresses. Repair of oral soft tissue defects that arise as a result of disease, trauma, or congenital abnormalities is often accomplished via transplantation or transfer of autologous mucosal tissue. However, this method of treatment can be complicated by the relatively small amount of autologous mucosal tissue that is available, as well as by the morbidity that may be associated with the donor site and patient reluctance to have oral (eg, palatal) surgery.

Generation of site-appropriate tissue by a living cellular sheet in the treatment of mucogingival defects.

Background: Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomic type, amount, and distribution of the tissue. This study is a post hoc analysis of data collected during previously published results from two randomized clinical trials of a living cellular sheet (LCS; allogenic cultured keratinocytes and fibroblasts in bovine collagen) versus a free gingival graft (FGG), evaluating their ability to augment keratinized tissue or gingiva.

Methods: Post hoc histologic and clinical (photographic) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two randomized clinical trials.

Living cellular construct for increasing the width of keratinized gingiva: results from a randomized, within-patient, controlled trial.

Background: The standard of care for increasing keratinized gingiva adjacent to teeth that do not require root coverage is the free gingival graft (FGG). A pilot study indicated that the use of a living cellular construct (LCC) could be effective in this clinical scenario.

Methods: A pivotal, multicenter, randomized, within-patient, controlled, open-label trial was conducted (N = 96 patients).

Periareolar mastopexy with FortaPerm.

Background: Recurrent ptosis is a common sequel of mastopexy. The use of mesh as an adjunct to the double-skin technique was developed to reduce the incidence of recurrent ptosis. The optimal mesh needs to strike the right balance between persistence, inflammation, biocompatibility, and incorporation without interfering with mammography or presenting a long-term infection risk.

Neurovascular congruence results from a shared patterning mechanism that utilizes Semaphorin3A and Neuropilin-1.

Peripheral nerves and blood vessels have similar patterns in quail forelimb development. Usually, nerves extend adjacent to existing blood vessels, but in a few cases, vessels follow nerves. Nerves have been proposed to follow vascular smooth muscle, endothelium, or their basal laminae.

The pattern of neurovascular development in the forelimb of the quail embryo.

Peripheral nerve and vascular patterns are congruent in the adult vertebrate, but this has been disputed in vertebrate embryos. The most detailed of these studies have used the avian forelimb as a model system, yet neurovascular anatomical relationships and critical vascular remodeling events remain inadequately characterized in this model. To address this, we have used a combination of intravascular marker injection, multilabel fluorescent stereomicroscopy, and confocal microscopy to analyze the spatiotemporal relationships between peripheral nerves and blood vessels in the forelimb of 818 quail embryos from E2 (HH13) to E15 (HH41).