Bridging small-gap peripheral nerve defects using acellular nerve allograft implanted with autologous bone marrow stromal cells in primates

Wang, Dong; Liu, Xiaolin; Jing, Zhu; Jiang, Li; Hu, Jun; Zhang, Yang; Yang, Limin; Wang, Honggang; Yi, Jianhua

doi:10.1016/j.brainres.2007.09.098

Cited by 115 publications

(88 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bone marrow stromal cells have attracted the attention of several groups interested in cellular strategies to supplement nerve repair. 10,12,20,26,54,64,70,75 These mesenchymal stem cells are harvested from the long bones, and when placed in culture medium containing the appropriate cytokine cocktail, 26 transdifferentiate into an adherent Schwann cell-like phenotype expressing S100 protein, GFAP, and p75. 12,64 They have been used with artificial conduits and acellular grafts, where they have contributed to improved electrophysiological, morphometric, and/or behavioral recovery outcomes versus vehicle controls.…”

Section: Sources Of Stem Cells For Peripheral Nerve Repairmentioning

confidence: 99%

Practical considerations concerning the use of stem cells for peripheral nerve repair

Walsh

Midha

2009

FOC

114

View full text Add to dashboard Cite

In this review the authors intend to demonstrate the need for supplementing conventional repair of the injured nerve with alternative therapies, namely transplantation of stem or progenitor cells. Although peripheral nerves do exhibit the potential to regenerate axons and reinnervate the end organ, outcome following severe nerve injury, even after repair, remains relatively poor. This is likely because of the extensive injury zone that prevents axon outgrowth. Even if outgrowth does occur, a relatively slow growth rate of regeneration results in prolonged denervation of the distal nerve. Whereas denervated Schwann cells (SCs) are key players in the early regenerative success of peripheral nerves, protracted loss of axonal contact renders Schwann cells unreceptive for axonal regeneration. Given that denervated Schwann cells appear to become effete, one logical approach is to support the distal denervated nerve environment by replacing host cells with those derived exogenously. A number of different sources of stem/precursor cells are being explored for their potential application in the scenario of peripheral nerve injury. The most promising candidate, transplant cells are derived from easily accessible sources such as the skin, bone marrow, or adipose tissue, all of which have demonstrated the capacity to differentiate into Schwann cell–like cells. Although recent studies have shown that stem cells can act as promising and beneficial adjuncts to nerve repair, considerable optimization of these therapies will be required for their potential to be realized in a clinical setting. The authors investigate the relevance of the delivery method (both the number and differentiation state of cells) on experimental outcomes, and seek to clarify whether stem cells must survive and differentiate in the injured nerve to convey a therapeutic effect. As our laboratory uses skin-derived precursor cells (SKPCs) in various nerve injury paradigms, we relate our findings on cell fate to other published studies to demonstrate the need to quantify stem cell survival and differentiation for future studies.

show abstract

Section: Sources Of Stem Cells For Peripheral Nerve Repairmentioning

confidence: 99%

Practical considerations concerning the use of stem cells for peripheral nerve repair

Walsh

Midha

2009

FOC

114

View full text Add to dashboard Cite

show abstract

“…To fulfill this requirement, additional factors have been incorporated into decellularized grafts such as cells (eg. Schwann cells and Mesenchymal stem cells (MSC)) (Wang et al, 2008;Wang et al, 2012;Zhang et al, 2010), growth factors (Hagg et al, 1991;Li et al, 2012) and gels . However, current decellularized grafts are limited due to the size of the basal laminal tubes (5-10µm), which are smaller than the typical diameter of cells (10-15μm).…”

Section: Introductionmentioning

confidence: 99%

Decellularized grafts with axially aligned channels for peripheral nerve regeneration

Sridharan

Reilly

Buckley

2015

Journal of the Mechanical Behavior of Biomedical Materials

View full text Add to dashboard Cite

At least 2 million people worldwide suffer annually from peripheral nerve injuries (PNI), with estimated costs of $7 billion incurred due to paralysis alone. The current "gold" standard for treatment of PNI is the autograft, which poses disadvantages such as high fiscal cost, possible loss of sensation at donor site and the requirement of two surgeries. Allografts are viable alternatives; however, intensive immunosuppressive treatments are often necessary to prevent host rejection. For this reason, significant efforts have been made to remove cellular material from allografts. These decellularized nerve grafts perform better than other clinically available grafts but not as well as autografts; therefore, current research on these grafts includes the incorporation of additional components such as growth factors and cells to provide chemical guidance to regenerating axons. However, effective cellular and axonal penetration is not achieved due to the small pore size (5-10μm) of the decellularized grafts.The overall objective of this study was to induce axially aligned channels in decellularized nerve grafts to facilitate enhanced cell penetration. The specific aims of this study were to optimize a decellularization method to enhance cellular removal, to induce axially aligned pore formation in decellularized grafts through a novel unidirectional freeze drying method, to study the bulk mechanical properties of these modified decellularized grafts and to assess cell penetration into these grafts. To this end we modified an existing decellularization protocol to improve cellular removal while preserving matrix structure in rat sciatic nerve sections. Standard freeze drying and unidirectional freeze drying were employed to impart the necessary pore architecture, and our results suggest that unidirectional freezing is a pertinent modification to the freeze drying process to obtain axially aligned channels. These highly porous scaffolds obtained using unidirectional freeze-drying possessed similar tensile properties to native nerve tissue and exhibited enhanced cellular penetration after 14 days of culture when compared to non-freeze dried and standard freeze-dried scaffolds. The results of this study not only highlight the importance of aligned pores of diameters ~20-60μm on cellular infiltration, but also presents unidirectional freeze drying as a viable technique for producing this required architecture in decellularized nerves. To the best of our knowledge, this study represents the first attempt to manipulate the physical structure of decellularized nerves to enhance cell penetration which may serve as a basis for future peripheral nerve regenerative strategies using decellularized allografts.

show abstract

“…They are also the most promising choice for the majority of clinical purposes. Bone marrow stromal cells have attracted the attention of many scientists interested in cellular strategies in the repair of neural tissue [78][79][80][81]. These mesenchymal stem cells are harvested from the long bones, and when placed in culture medium containing the appropriate cytokine cocktail, transdifferentiate into Schwann cell-like phenotype [82].…”

Section: Bone As a Source Of Adult Stem Cellsmentioning

confidence: 99%

Bone as a source of organism vitality and regeneration

Mackiewicz¹,

Niklińska²,

Kowalewska³

et al. 2012

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:The most important features that determine the vital role of bone include: a) a continuous supply of calcium, which is indispensible for every cell of the entire organism at all times, and b) the delivery of circulating blood cells and some adult stem cells to keep the body vigorous, ready for self-reparation, and continuously rebuilding throughout life. These functions of bones are no less important than protecting the body cavities, serving as mechanical levers connected to the muscles, and determining the shape and dimensions of the entire organism. The aim of this review was to address some basic cellular and molecular knowledge to better understand the complex interactions of bone structural components. The apprehension of osteoblast differentiation and its local regulation has substantially increased in recent years. It has been suggested that osteocytes, cells within the bone matrix, act as regulatory mechanosensors. Therefore immobility as well as limited activity has a dramatic effect on bone structure and influences a broad spectrum of bone physiology-related functions as well as the functions of many other organs. Lifelong bone rebuilding is modulated through several pathways, including the Wnt pathway that regulates bone formation and resorption. In the adult skeleton, bone is continuously renewed in response to a variety of stimuli, such as the specific process of remodeling dependent on RANK/ /RANKL/OPG interactions. Better understanding of bone biology provides opportunities for the development of more effective prevention and treatment modalities for a variety of bone diseases, including new approaches to adult stem cell-based therapies.

show abstract

Bridging small-gap peripheral nerve defects using acellular nerve allograft implanted with autologous bone marrow stromal cells in primates

Cited by 115 publications

References 28 publications

Practical considerations concerning the use of stem cells for peripheral nerve repair

Practical considerations concerning the use of stem cells for peripheral nerve repair

Decellularized grafts with axially aligned channels for peripheral nerve regeneration

Bone as a source of organism vitality and regeneration

Contact Info

Product

Resources

About