Mikinori Ikeda

Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair.

In spite of the extensive research using induced pluripotent stem (iPS) cells, the therapeutic potential of iPS cells in the treatment of peripheral nerve injury is largely unknown. In this study, we repaired peripheral nerve gaps in mice using tissue-engineered bioabsorbable nerve conduits coated with iPS cell-derived neurospheres. The secondary neurospheres derived from mouse iPS cells were suspended in each conduit (4000,000 cells per conduit) and cultured in the conduit in three-dimensional (3D) culture for 14 days. We then implanted them in the mouse sciatic nerve gaps (5 mm) (iPS group; n=10). The nerve conduit alone was implanted in the control group (n=10). After 4, 8 and 12 weeks, motor and sensory functional recovery in mice were significantly better in the iPS group. At 12 weeks, all the nerve conduits remained structurally stable without any collapse and histological analysis indicated axonal regeneration in the nerve conduits of both groups. However, the iPS group showed significantly more vigorous axonal regeneration. The bioabsorbable nerve conduits created by 3D-culture of iPS cell-derived neurospheres promoted regeneration of peripheral nerves and functional recovery in vivo. The combination of iPS cell technology and bioabsorbable nerve conduits shows potential as a future tool for the treatment of peripheral nerve defects.

Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system

Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable nerve conduits have been explored as options for peripheral nerve repair. However, no reports of nerve conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral nerves. In the present study, sciatic nerve gaps in mice were reconstructed in the following groups: nerve conduit alone (control group), nerve conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), nerve conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral nerve regeneration using nerve conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable nerve conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral nerve regenerative therapy.

A tissue-engineered bioabsorbable nerve conduit created by three-dimensional culture of induced pluripotent stem cell-derived neurospheres

We previously reported a bioabsorbable nerve conduit coated with Schwann cells for the treatment of peripheral nerve defects. Since there have been dramatic developments in induced pluripotent stem (iPS) cells in recent years, the purpose of the present study was to create a tissue-engineered nerve conduit coated with iPS cell-derived neurospheres. Such a conduit was constructed by three-dimensional (3D)-culture of these cells using a bioabsorbable polymer conduit as a scaffold. The nerve conduit was composed of a mesh of poly L-lactide, and a porous sponge of 50% poly L-lactide and 50% poly ε-caprolactone. The primary and secondary neurospheres (PNS and SNS, respectively) induced from iPS cells were suspended in individual conduits. The conduits were incubated for 7 or 14 days in vitro and then evaluated using immunohistochemistry. All of the 7- and 14-day differentiated PNS and SNS were observed to have adhered to the inner surface of the conduits and to have migrated into the inner porous sponge. The engrafted cells were positive for anti-Tuj1, -S-100 and -GFAP antibodies, indicating that their pluripotent ability to form neural or glial cells was maintained. These findings indicate the feasibility of creating nerve conduits coated with a 3D-culture of iPS cell-derived neurospheres for the treatment of peripheral nerve defects.

Long-term efficacy and safety outcomes of transplantation of induced pluripotent stem cell-derived neurospheres with bioabsorbable nerve conduits for peripheral nerve regeneration in mice.

The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable nerve conduits coated with iPSc-derived neurospheres for use in peripheral nerve repair. Here, we examine the long-term efficacy and safety of using nerve conduits with iPSc technology for peripheral nerve repair in mice. The nerve conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% ε-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the nerve conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the nerve conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable nerve conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable nerve conduits has the potential to be a safe future tool for the treatment of peripheral nerve defects.

A propeller flap based on the thoracoacromial artery for reconstruction of a skin defect in the cervical region: A case report

A propeller flap is useful for coverage of an adjacent skin defect without dissection back to source vessels and harvesting muscle tissues. The thoracoacromial artery is one of the vascular pedicles of the flaps for reconstruction in the cervical region. Use of a propeller flap based on the thoracoacromial artery has not previously been reported for reconstruction in the cervical region. We report a case in which a propeller flap based on the thoracoacromial artery was used for skin coverage after tumour resection in the cervical region together with an anatomical investigation. The propeller flap based on the thoracoacromial artery was harvested in the supine position, requiring no change in position after tumour resection. The skin defect was successfully reconstructed using the propeller flap based on the thoracoacromial artery with linear closure of the donor site. The propeller flap based on the thoracoacromial artery offers an alternative for reconstruction in the cervical region.

Intraneural nodular fasciitis of the median nerve: case report and literature review.

Nodular fasciitis, a benign soft tissue tumor, occurs most frequently in the forearm and is generally divided into subcutaneous, intramuscular, and fascial types. Intraneural nodular fasciitis has been reported in only 5 patients previously. We present the case of a 79-year-old woman with nodular fasciitis within the median nerve at the proximal forearm. Carpal tunnel syndrome was suspected at the initial visit, but high median nerve palsy and a mass at the proximal forearm were found a few months later. Subtotal resection of the tumor within the median nerve was performed and histological diagnosis indicated nodular fasciitis. There was no evidence of recurrence at follow-up 1 year and 3 months after surgery. Motor weakness had resolved but sensation was compromised.

Outcome of the Sauvé–Kapandji procedure for distal radioulnar joint disorder with rheumatoid arthritis or osteoarthritis: Results of one-year follow-up

Abstract Objectives: We performed the Sauvé–Kapandji procedure for treating disorders of the distal radioulnar joint (DRUJ) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). This study aimed to compare and clarify the results of the SK procedure between RA and OA patients. We report the one-year follow-up results of patients who underwent the SK procedure to correct the DRUJ disorder caused by RA or OA. Methods: The study included 22 wrists of 19 patients with RA and 10 wrists of nine patients with OA. Pain, grip strength and range of motion of the wrist were examined clinically. For the evaluation of the stability of the carpus, ulnar stump and bone union, parameters were measured using radiographs. Shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH) was used for functional evaluation. Results: Wrist pain reduced in all cases, and bone union was achieved in all wrists. The QuickDASH score significantly improved in both patients with RA and OA. In patients with RA, the range of motion increased significantly with regard to supination but decreased significantly with regard to palmar flexion. Carpal alignment and ulnar stump stability were maintained well at one-year follow-up. Conclusion: The Sauvé–Kapandji procedure for treating disorders of the distal radioulnar joint DRUJ showed good results clinically and radiographically, irrespective of RA or OA.

Pedicled Adipose Tissue for Treatment of Chronic Digital Osteomyelitis

PURPOSE To describe a surgical technique (pedicled vascularized tissue transfer) for treating chronic digital osteomyelitis. METHODS Adipose tissue was obtained at the level of the proximal phalanx based on anterograde or retrograde flow. After bone debridement, we inserted the vascularized adipose tissue into the dead space. Eight patients were treated with this procedure from 2009 to 2012. One patient had chronic osteomyelitis in the thumb, 4 in the index finger, 2 in the middle finger, and 1 in the ring finger. Foci of chronic osteomyelitis were located at the distal phalanx in 2 patients, at the distal to middle phalanx across the distal interphalangeal joint in 4, at the middle phalanx in 1, and at the proximal phalanx in 1. Mean duration of follow-up was 41 months. We assessed the efficacy of the technique by clinical symptoms and imaging. RESULTS We used retrograde pedicled adipose tissue transfer in 7 patients and anterograde pedicled adipose tissue transfer in 1. The pedicled adipose tissue was successfully transferred from the digit tip to its base. The postoperative courses were uneventful; no additional treatments were required. Postoperative physical data and follow-up images showed no evidence of chronic osteomyelitis. No functional loss was caused by procuring vascularized adipose tissue from the digits. CONCLUSIONS Pedicled vascularized tissue transfer based on the digital artery was a reliable and reproducible technique. We recommend it as a treatment option for chronic digital osteomyelitis. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Entrapment of Digital Nerves due to an Embedded Ring: A Case Report

Chronic embedded ring injury, which has a very dramatic appearance, is very rare, with only approximately 20 cases previously reported in the English literature.1–10 In most of the reported cases, the ring was simply removed with a ring cutter in the emergency setting, and few surgical interventions were required. There have been only a few reports of sensory disturbance of the finger with an embedded ring.2,4,8 However, the appearances of the digital nerves have never been confirmed with a surgical procedure when the ring was removed. This is the first case report of a chronic embedded ring injury in which severe constriction of the digital nerves by the embedded ring was demonstrated on surgical exploration, and atraumatic neurolysis of the digital nerves was required. A 73-year-oldwoman presentedwith an embedded ring in her right ring finger, with swelling and foul discharge after a blow. She had been wearing the ring for more than 20 years, and the ring had been embedded for 10 years. She had previously received psychotherapy and had taken orally antianxiety agents for few years, but she was on no drugs at the time of presentation. The patient reported that she had gained weight from 38 kg early in life to 62 kg recently. On examination, only the dorsal part of the ring could be seen above the skin dorsally, and an intact bridge of skin overlaid the volar aspect of the ring (►Fig. 1). The ring finger was swollen with foul discharge, but the distal circulation was satisfactory. The range of motion was limited to moderate flexion. On neurological examination, although there was no numbness, sensation distal to the buried ring was diminished: SemmesWeinstein monofilament values were 4.56 on the ulnar side and 4.31 on the radial side; static two-point discrimination values were 10 mm on the ulnar side and 8 mm on the radial side. Plain radiographs of the ring finger showed the completely buried ring within the volar soft tissue, but bone scalloping was not appreciable in the proximal phalanx (►Fig. 2). Surgical exploration was performed under brachial plexus anesthesia to avoid damaging the neurovascular bundles during removal of the ring. A Brunner zigzag incision was made on the volar aspect of the ring finger. The neurovascular bundles, especially the digital nerves, were extremely entrapped between the ring and the proximal phalanx (►Fig. 3), and theflexor digitorumprofundus tendonwas ruptured. The neurovascular bundles were released carefully, and then the ring was removed safely after opening the stems of the ring without using a ring cutter because of the divided original design of the bottom of the ring (►Fig. 4). The hypertrophic granulation tissue at the entrance wounds was debrided, and the skin was primarily closed. The wound healed uneventfully with oral antibiotic coverage. About 1 year and 7 months after the surgery, the sensory disturbance of the finger improved without numbness; Semmes Weinstein monofilament values were 3.61 on the ulnar side and 2.83 on the radial side, and static two-point discrimination valueswere 7 mmon the ulnar side and 6 mm on the radial side. Although we recommended additional tendon reconstruction of the flexor digitorum profundus, she refused it and was left with restricted flexion of the distal interphalangeal joint. In the early stage of the embedded ring, the digital skin is still intact, althoughminor abrasion can occur, and the ring is very tight and barely mobile.6 As the condition progresses, the skin and subcutaneous tissue are eroded with low-grade infection, and then part of the volar skin starts healing. As time goes by, the ring becomes gradually embedded into the finger with only the dorsal surface exposed. In the final stage, the soft tissue, flexor and extensor tendons, digital nerves, and phalangeal bone become involved. Because the digital

Comparison of Median Nerve Cross-sectional Area on 3-T MRI in Patients With Carpal Tunnel Syndrome

This study correlated morphologic abnormalities of idiopathic carpal tunnel syndrome (CTS) with the severity of CTS using 3-T magnetic resonance imaging (MRI). The relationship of the severity of CTS and the cross-sectional area of the median nerve (CSA) was assessed at several levels. Seventy wrists of 35 patients (27 women and 8 men) with unilateral idiopathic CTS underwent nerve conduction study and 3-T MRI of the wrist. The CSA at 4 levels (distal radioulnar joint, body of scaphoid, tubercule of scaphoid, and hook of hamate) and the thickness of the transverse carpal ligament at 3 levels in both affected and unaffected hands were measured using 3-T MRI and correlated with the severity of CTS assessed with distal motor latency. The CSA in the affected hand at the scaphoid body level was significantly higher than in the unaffected hand. The CSA at the scaphoid body level was positively correlated with distal motor latency in the affected hand. The CSA in the affected hand at the scaphoid tubercule level was significantly lower than in the unaffected hand. The CSA had a negative correlation with distal motor latency at the scaphoid tubercule level. The CSA at the distal radioulnar joint and the hamate hook was not significantly different between the affected hand and the unaffected hand. The CSA at the distal radioulnar joint level and hook level were not correlated significantly with distal motor latency in the affected hand. The mean CSA of the affected hand at the scaphoid body level was highest in 4 levels. [Orthopedics. 2017; 40(1):e77-e81.].