Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.

For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40-80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 10(3)-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs.

Treatment of a Large Nail-Bed Pyogenic Granuloma with Topical Timolol.

Nail pyogenic granulomas are common benign vascular lesions often occurring after trauma. A variety of treatment modalities exist, including topical therapies and surgical excision, although both have their pros and cons. In this communication, we describe the case of a 7-year-old boy with repeated toe trauma, who developed a large nail bed pyogenic granuloma after undergoing surgical debridement and nail bed repair. He was treated with 3 months of topical 0.5% timolol maleate, resulting in complete resolution of the pyogenic granuloma and minimal nail deformity.

Novel Use of an Internal Distractor for Metacarpal Lengthening.

BACKGROUND: In patients who have had proximal digit amputation, metacarpal distraction osteogenesis is an option to improve digital length and function. One drawback is that traditional external distraction devices are large and cumbersome; the option of a low-profile internal device is therefore appealing. Internal distractors are commonly used in craniofacial reconstruction, but use in the hand has not been reported. We describe a case series of the novel use of an internal distractor in metacarpal lengthening. METHODS: In this single-center case series, patients who underwent metacarpal distraction by the senior author using a uniplanar internal distractor were reviewed, and indications, outcomes, and complications were analyzed. RESULTS: There were 5 cases in 4 patients (age range: 7-33 years). Indications were traumatic amputation in 4 cases and congenital hypoplasia in 1. All were successfully distracted, with a mean final length gain of 1.3 cm (range: 1.0-1.7 mm). Mean time from device placement to consolidation was 3.5 months. Complications included activation arm site infection in 2 cases, both occurring after the distraction period, necessitating device removal before full consolidation. In these cases, the device was removed after the distraction period and replaced with a Kirschner wire for stabilization through the consolidation period. CONCLUSIONS: Metacarpal distraction was successfully achieved with an internal distraction device. Although infection was common, it occurred after the distraction period and did not preclude length gain. We feel that this low-profile device offers advantages over cumbersome external devices typically used for metacarpal lengthening.

Multipotent adult progenitor cells sustain function of ischemic limbs in mice.

Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.

Extending the Reach of Craniofacial Free Flaps Using the Descending Branch of the Lateral Circumflex Femoral Vessels.

SUMMARY: Craniofacial free tissue transfer is sometimes complicated by insufficient pedicle length and/or paucity of recipient vessels. A saphenous vein graft can be used to reach the high-flow, large-caliber vessels of the neck, but because of the vein's taper and thick wall, there is often a mismatch. Following the principle of like-for-like, the authors prefer the descending branch of the lateral circumflex femoral vessels to achieve a more anatomical pedicle extension for free tissue transfer in complex craniofacial reconstruction. The authors' experience using the descending branch of the lateral circumflex femoral pedicle extender from 2010 to 2019 was reviewed. Indications, patient characteristics, reconstruction site, flap type, pedicle length, recipient vessels, and vascular complications were noted. The authors reviewed two strategies for implementation of the pedicle extender: in some cases, the flap was first transferred and allowed to perfuse on the descending branch of the lateral circumflex femoral vessels in the thigh, and then transferred to the recipient vessels (double-ischemia transfer); and in other cases, the flap and pedicle extender were transferred such that the flap underwent a single period of ischemia (single-ischemia transfer). The descending branch of the lateral circumflex femoral pedicle extender was used in 17 craniofacial cases. Indications included tumor, trauma, osteoradionecrosis, and congenital. Double-ischemia transfer was used in eight cases and single-ischemia transfer in nine. The longest pedicle extender in the series was 15 cm. Arterial thrombosis occurred in one case. This case series demonstrates that the descending branch of the lateral circumflex femoral pedicle extender is a viable option for complex craniofacial free tissue transfer cases. It provides ample length and excellent vessel match, following the like-for-like principle. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Interdisciplinary Management of Minimally Displaced Orbital Roof Fractures: Delayed Pulsatile Exophthalmos and Orbital Encephalocele.

Traumatic orbital roof fractures are rare and are managed nonoperatively in most cases. They are typically associated with severe mechanisms of injury and may be associated with significant neurologic or ophthalmologic compromise including traumatic brain injury and vision loss. Rarely, traumatic encephalocele or pulsatile exophthalmos may be present at the time of injury or develop in delayed fashion, necessitating close observation of these patients. In this article, we describe two patients with minimally displaced blow-in type orbital roof fractures that were later complicated by orbital encephalocele and pulsatile exophthalmos, prompting urgent surgical intervention. We also suggest a management algorithm for adult patients with orbital roof fractures, emphasizing careful observation and interdisciplinary management involving plastic surgery, neurosurgery, and ophthalmology.

A novel in-vitro system for the simultaneous exposure of bladder smooth muscle cells to mechanical strain and sustained hydrostatic pressure.

The novel hydrostrain system was designed in an effort to establish and maintain conditions that simulate the in-vivo mechanical environment of the bladder. In this laboratory system, ovine bladder smooth muscle cells on flexible, 10-cm-dia silastic membranes were exposed simultaneously to hydrostatic pressure (40 cm H2O, a pressure level currently associated with bladder pathologies) and mechanical strains (up to 25 percent) under standard cell culture conditions for 7 h. Under these conditions, Heparin Binding-Epidermal Growth Factor and Collagen Type III mRNA expression were significantly increased (p<0.01 and 0.1, respectively); however, no changes were observed in Collagen Type I mRNA expression. Decreases in the Collagen Type I:Type III ratio following simultaneous exposure of bladder smooth muscle cells to pathological levels of hydrostatic pressure and mechanical strain in vitro are in agreement with clinically observed increases in Collagen Type III with concomitant decreased human bladder compliance. The results of the present study, therefore, provide cellular/molecular level information relevant to bladder pathology that could have significant implications in the field of clinical urology.