Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele

E Shapiro  1 , M J Seller, H Lepor, D K Kalousek, G M Hutchins, E J Perlman, M Meuli

Purpose: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation.

Journal: The Journal of Urology: 1998 Sep;160(3 Pt 2):1047-53; discussion 1079

Date: 01/09/1998

1 Department of Urology, New York University School of Medicine, New York, USA.

Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model

R S Namba  1 , M Meuli, K M Sullivan, A X Le, N S Adzick

A fetal lamb model was developed to investigate the capacity of fetal articular cartilage for repair after the creation of a superficial defect. Superficial defects, 100 micrometers deep, were made in the articular cartilage of the trochlear groove in the distal aspect of the femur in eighteen fetal lambs that were halfway through the 145-day gestational period; the contralateral limb was used as a sham control. The wounds were allowed to heal in utero for three, seven, fourteen, twenty-one, or twenty-eight days. Seven days after the injury, the defects were filled with a hypocellular matrix, which stained lightly with safranin O. At twenty-eight days, the staining of the matrix was similar to that of the sham controls and the chondrocyte density and the architectural arrangement of the cell layers had been restored. An inflammatory response was not elicited, and no fibrous scar tissue was observed.

Journal: The Journal of Bone & Joint Surgery, American Volume: 1998 Jan;80(1):4-10

Date: 01/01/1998

1 Department of Orthopaedic Surgery, University of California at San Francisco, 94143-0728, USA.

Latissimus dorsi flap procedures to cover myelomeningocele in utero: a feasibility study in human fetuses

Claudia Meuli-Simmen a, b, c, d Martin Meuli a, b, c, d N. Scott Adzick a, b, c, d Michael R Harrison a, b, c, d

There is experimental and clinical evidence that in utero repair of myelomeningocele (MMC) may preserve neurological function. In five aborted human fetuses (gestational age, 18 to 29 weeks), the authors tested whether proximally and distally based latissimus dorsi flaps (LDF) can be used to cover MMC lesions. Fetal soft tissues were developed enough to allow surgical handling, preparation of both flap types was technically easy, and the vascular pedicles could be preserved. The proximally pedicled LDF was suitable to cover the upper spine from lower cervical to lower thoracic levels, whereas the distally pedicled LDF was suitable to cover the spine between lower thoracic and lower sacral levels. These results suggest that various LDF procedures are technically feasible in early gestational human fetuses and could be used for in utero repair of MMC.

Journal: Journal of Pediatric Surgery (Volume 32, Issue 8, Pages 1154-1156)

Date: 01/08/1997

a Division of Hand, Plastic, and Reconstructive Surgery, University Children's Hospital, Zurich, Switzerland.

b the Department of Surgery, University Children's Hospital, Zurich, Switzerland.

c The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA

d The Fetal Treatment Center, University of California, San Francisco, CA, USA


The spinal cord lesion in human fetuses with myelomeningocele: Implications for fetal surgery

Martin Meuli a, b, c, d, e, f Claudia Meuli-Simmen a, b, c, d, e, f Grover M Hutchins a, b, c, d, e, f Mary J Seller a, b, c, d, e, f Michael R Harrison a, b, c, d, e, f N. Scott Adzick a, b, c, d, e, f

Recently produced experimental evidence suggests that secondary traumatic injury and degenerative changes, acquired in utero, to the openly exposed neural tissue may be primarily responsible for the massive neurological deficit associated with myelomeningocele (MMC). The goal of this study was to examine the morphology of human fetuses with MMC to determine if acquired trauma to the spinal cord could be identified. The MMC lesions with surrounding tissues from 10 human fetuses ranging in gestational age between 19 and 23 weeks were prepared with serial histological sections. The MMC lesions were characterized by an open vertebral arch, an open dura mater fused laterally to the dermis, and an open pia mater fused laterally to the epidermis. The spinal cord was exposed, without any meningeal, bony, or cutaneous covering, and was resting on the dorsal aspect of the abnormal arachnoid sac created by the fusion of the meninges to the cutaneous tissues. The exposed neural tissue had undergone varying degrees of recent traumatic injury as a result of its exposed position, ranging from nearly complete preservation of neural elements in four cases to nearly complete loss in two cases. The neural tissue remaining in the MMC with partial loss contained hemorrhages and abrasions from recent injury, suggesting that injury occurred during passage through the birth canal. The presence of dorsal and ventral parts of the cord with nerve roots and ganglia demonstrated that these structures had formed during development and that the loss of tissue by injury was a secondary change. The results support the concept that performing in utero surgery could protect the exposed but initially well-developed and uninjured cord, prevent secondary neural injury, and preserve neural function in the human fetus with myelomeningocele.

Journal: Journal of Pediatric Surgery (Volume 32, Issue 3, Pages 448-452)

Date: 01/03/1997

a Department of Surgery, University Children's Hospital, Zurich, Switzerland

b the Division of Hand, Plastic, and Reconstructive Surgery, University Hospital, Zurich, Switzerland

c the Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

d the Division of Medical and Molecular Genetics, Guy's Hospital, London, England

e The Fetal Treatment Center, University of California, San Francisco, CA, USA

f the Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

Midgestational sciatic nerve transection in fetal sheep results in absent nerve regeneration and neurogenic muscle atrophy

C Meuli-Simmen  1 , M Meuli, C D Yingling, T Eiman, G B Timmel, H J Buncke, W Lineaweaver, M R Harrison, N S Adzick  

In order to test whether fetal nerve healing and regeneration result in complete functional recovery, we transected the sciatic nerve at trunk level in 13 midgestational sheep fetuses. In 10 fetuses immediate microsurgical nerve coaptation was performed. The neonatal lambs were evaluated clinically, electrophysiologically, and histologically. On the transected side, the 10 surviving lambs showed a sensorimotor sciatic nerve paralysis and atrophy of the muscles innervated by the sciatic nerve. Somatosensory evoked potentials were weakly present in 5 animals and absent in 5 animals. Histologically, minimal signs of axonal regeneration, massive degeneration of the entire nerve, and a marked neurogenic muscle atrophy were found. These unexpected results differ from the findings after peripheral nerve transections in late gestational sheep fetuses and also from the classic wallerian degeneration-regeneration pattern that follows adult nerve injury. We speculate that the almost absent regenerative potential at midgestation is related to axotomy-induced neurotrophic factor deprivation during a developmental phase where the neurons are critically dependent on growth factor for survival.

Journal: Plastic and Reconstructive Surgery 1997 Feb;99(2):486-92.

Date: 01/02/1997

1 Fetal Treatment Center, University of California, San Francisco, USA.