Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo

Lopatina, Tatiana; Ni, Kalinina; Karagyaur, Maxim; Stambolsky, Dmitry; Рубина, К. А.; Revischin, Alexander; Pavlova, Galina; Parfyonova, Yelena; Tkachuk, Vsevolod A.

doi:10.1371/journal.pone.0017899

Cited by 253 publications

(221 citation statements)

References 32 publications

(40 reference statements)

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“…In addition, exogenous NGF rescues cholinergic neurons in the basal forebrain and improves cognitive function in aged animals (Markowska et al, 1994), and NSCs overexpressing NGF restore memory deficits in AD model animals (Lee et al, 2012). Indeed, ADMSCs secrete various growth/neurotrophic factors, including BDNF and NGF (Kim et al, 2010;Lopatina et al, 2011). BDNF and NGF stimulate cholinergic phenotypes by increasing ChAT activity in cultures enriched with embryonic rat motor neurons (Wong et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…ADMSCs secrete various growth/neutrophic factors such as NGF, BDNF, and vascular endothelial growth factor, so it is expected that these cells might exert neuroprotective activity and thereby improve body functions in aged animals (Kim et al, 2010;Lopatina et al, 2011). In the present study, we investigated the recovery effects of ADMSCs on cognitive and neurobehavioral dysfunctions in aged mice.…”

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confidence: 93%

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Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Park

Yang

Bae

et al. 2013

J of Neuroscience Research

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Brain ageing leads to atrophy and degeneration of the cholinergic nervous system, resulting in profound neurobehavioral and cognitive dysfunction from decreased acetylcholine biosynthesis and reduced secretion of growth and neurotrophic factors. Human adipose tissue-derived mesenchymal stem cells (ADMSCs) were intravenously (1 3 10 6 cells) or intracerebroventricularly (4 3 10 5 cells) transplanted into the brains of 18-month-old mice once or four times at 2-week intervals. Transplantation of ADMSCs improved both locomotor activity and cognitive function in the aged animals, in parallel with recovery of acetylcholine levels in brain tissues. Transplanted cells differentiated into neurons and, in part, into astrocytes and produced choline acetyltransferase proteins. Transplantation of ADMSCs restored microtubule-associated protein 2 in brain tissue and enhanced Trk B expression and the concentrations of brain-derived neurotrophic factor and nerve growth factor. These results indicate that human ADMSCs differentiate into neural cells in the brain microenvironment and can restore physical and cognitive functions of aged mice not only by increasing acetylcholine synthesis but also by restoring neuronal integrity that may be mediated by growth/neurotrophic factors. V V C 2013 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 93%

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Park

Yang

Bae

et al. 2013

J of Neuroscience Research

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“…Undifferentiated rat ASC have also been shown to enhance peripheral nerve repair [28,30], and they may act synergistically with Schwann cells to secrete growth factors such as NGF [25]. Alternatively, the stem cells can be neurally induced to release enhanced levels of BDNF, which is necessary for their nerve stimulatory effects [27]. This may also account for our improved results using stimulated human ASC.…”

Section: Stimulated Asc Enhance Nerve Repairmentioning

confidence: 97%

“…Transplantation of rat ASC in nerve conduits promotes nerve regeneration, enhances nerve conduction velocities, and reduces muscle atrophy and sensory neuron cell death after sciatic nerve injury [25][26][27][28][29][30]. To date, only a few reports show these results can be replicated using human ASC.…”

mentioning

confidence: 99%

Stimulating the Neurotrophic and Angiogenic Properties of Human Adipose-Derived Stem Cells Enhances Nerve Repair

Kingham

Kolar

Novikova

et al. 2014

Stem Cells and Development

183

147

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“…It is also extensively used to anastomose lesioned peripheral nerves [190,[262][263][264][265][266][267][268][269][270][271][272][273]. In fact, fibrin glue is a better for anastomosing peripheral nerves than sutures [268,[273][274][275][276][277].…”

Section: Pure Fibrin and Platelet-rich Fibrin Glue For Peripheral Nermentioning

confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo

Cited by 253 publications

References 32 publications

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Stimulating the Neurotrophic and Angiogenic Properties of Human Adipose-Derived Stem Cells Enhances Nerve Repair

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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