Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabol... more Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators. Chondrocytes from nine non-osteoarthritic patients and from six osteoarthritic (OA) donors at the time of total knee arthroplasty were chondro-differentiated in pellets for 2 weeks. Non-OA pellets were exposed for 72 hours to IL-1β/TNF-α and then cultured up to 14 days in 2 % FBS-supplemented NCCM or 2 % FBS-supplemented medium (control (ctr)). OA pellets were cultured in NCCM or ctr medium without ...
Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerativ... more Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.
The Journal of the Canadian Chiropractic Association, 2014
Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, o... more Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD's contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes.
Non-chondrodystrophic dog notochord cell conditioned medium was used to evaluate chondrocyte prot... more Non-chondrodystrophic dog notochord cell conditioned medium was used to evaluate chondrocyte proteoglycan production and cell proliferation. To evaluate the responsiveness of bovine disc-derived chondrocytes to notochord-cell conditioned medium with respect to proteoglycan and cell proliferation. In addition, to examine phenotypic changes of notochord cells cultured in monolayered as compared to 3-dimensional culture. Non-chondrodystrophic dogs maintain their intervertebral disc notochord cells into adulthood and are protected from having degenerative disc disease develop. The chondrodystrophic breeds such as beagles do not preserve these cells and have disc disease develop much earlier in life. The role of the notochord cell within the disc nucleus is poorly understood. Canine notochord cells were cultured within alginate beads in serum-deficient conditions using Dulbecco modified Eagle medium to produce notochord cell conditioned medium (NCCM). NCCM was used to stimulate bovine disc chondrocytes from which we evaluated proteoglycan production and cell proliferation as compared to chondrocytes grown in DMEM alone. In addition, parallel cultures of notochord cells were seeded within alginate beads as well as in monolayer and cultured in order to examine for differences in phenotype between the 2 culture conditions. The morphologic aspects of the intervertebral disc between the species differed markedly. A dose- dependent relationship was seen between proteoglycan production and NCCM concentration across various concentrations of NCCM in repeated experiments. Although there was a 4-fold increase in cell proliferation under all NCCM concentrations, this increase in cell proliferation was not dose dependent in the concentrations tested. Unlike chondrocytes, notochord cells do not adhere to tissue culture plate (monolayer) until at least day 4-6, do not markedly alter their phenotype, and rapidly assume masses of cells while floating within tissue culture medium. The biology of the disc-derived chondrocyte is profoundly affected by NCCM in that various concentrations of NCCM activate proteoglycan production in a dose-dependent fashion. However, in the doses tested in our study, cell proliferation was increased but in a nondose-dependent fashion. Notochord cells retain their phenotype even in monolayer and through the development of floating intimately associated masses of cells suggest the development and maintenance of cell-cell interaction. These masses of cells are retained even after 6 days in culture when they do attach to the tissue plate surface. The persistence of notochord cells in non-chondrodystrophic dog species suggests that these in vitro studies may mirror the milieu of the disc in vivo, in which the notochord cell may play a key role in disc homeostasis.
Systematic review. We sought to answer the following clinical questions: (1) Is structured exerci... more Systematic review. We sought to answer the following clinical questions: (1) Is structured exercise more effective in the treatment of chronic low back pain (LBP) than spinal manipulative therapy (SMT)? (2) Is structured exercise more effective in the treatment of chronic LBP than acupuncture? (3) Is SMT more effective in the treatment of chronic LBP than acupuncture? (4) Do certain subgroups respond more favorably to specific treatments? (5) Are any of these treatments more cost-effective than the others? Exercise, SMT, and acupuncture are widely used interventions in the treatment of chronic LBP. There is evidence that all of these approaches may offer some benefit for patients with chronic LBP when compared with usual care or no treatment. The relative benefits or cost-effectiveness of any one of these treatments when compared with the others are less well-defined, and it is difficult to identify specific subgroups of those with chronic LBP who may preferentially respond to a particular treatment modality. A systematic review of the literature was performed to identify randomized controlled trials comparing a structured exercise program, SMT, or acupuncture with one another in patients with chronic LBP. Two studies were identified comparing the use of structured exercise with SMT that met our inclusion criteria. Although these studies utilized different approaches for the exercise and SMT treatment groups, patients in both groups improved in terms of pain and function in both studies. Using random-effects modeling, there was no difference between the exercise and SMT groups when the data from these studies were pooled. We identified no studies meeting our inclusion criteria that compared acupuncture with either structured exercise or SMT or that addressed the relative cost-effectiveness of these approaches in the treatment of patients with chronic LBP. The studies identified indicate that structured exercise and SMT appear to offer equivalent benefits in terms of pain and functional improvement for those with chronic LBP with clinical benefits evident within 8 weeks of care. However, the level of evidence is low. There is insufficient evidence to comment on the relative benefit of acupuncture compared with either structured exercise or SMT or to address the differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is also insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP. Structured exercise and SMT appear to offer equivalent benefits in the management of pain and function for patients with nonspecific chronic LBP. If no clinical benefit is appreciated after using one of these approaches for 8 weeks, then the treatment plan should be reevaluated and consideration should be given to modifying the treatment approach or using alternate forms of care. Strength of recommendation: Weak.There is insufficient evidence regarding the relative benefits of the acupuncture compared with either structured exercise or SMT in the treatment of chronic LBP.There is insufficient evidence to address differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP.
Systematic review. To conduct a systematic review investigating the evidence of (1) efficacy, eff... more Systematic review. To conduct a systematic review investigating the evidence of (1) efficacy, effectiveness, and safety of nonoperative treatment of patients with cervical myelopathy; (2) whether the severity of myelopathy affects outcomes of nonoperative treatment; and (3) whether specific activities or minor injuries are associated with neurological deterioration in patients with myelopathy or asymptomatic stenosis being treated nonoperatively. Little is known about the appropriate role of nonoperative treatment in the management of cervical myelopathy, which is typically considered a surgical disorder. A systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 20, 2012. We included all articles that compared nonoperative treatments or observation with surgery for patients with cervical myelopathy or asymptomatic cervical cord compression to determine their effects on clinical outcomes, including myelopathy scales (Japanese Orthopaedic Association, Nurick), general health scores (36-Item Short Form Health Survey), and pain (neck and arm). Nonoperative treatments included physical therapy, medications, injections, orthoses, and traction. We also searched for articles evaluating the effect of specific activities or minor trauma in neurological outcomes. Case reports and studies with less than 10 patients in the exposure group were excluded. Of 54 citations identified from our search, 5 studies reported in 6 articles met inclusion criteria. In 1 randomized controlled study, there was low evidence that nonoperative treatment may yield equivalent or better outcomes than surgery in those with mild myelopathy. For moderate to severe myelopathy, nonoperative treatment had inferior outcomes versus surgery in 2 cohort studies, despite the fact that surgically treated patients were worse at baseline. There was insufficient evidence to determine whether specific activities or minor trauma is a risk factor for neurological deterioration in those with myelopathy or asymptomatic cord compression. There is a paucity of evidence for nonoperative treatment of cervical myelopathy, and further studies are needed to determine its role more definitively. In particular, for the patient with milder degrees of myelopathy, randomized studies comparing nonoperative with surgical treatment would be particularly helpful, as would trials comparing specific types of nonoperative treatments with the natural history of myelopathy. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: Because myelopathy is known to be a typically progressive disorder and there is little evidence that nonoperative treatment halts or reverses its progression, we recommend not routinely prescribing nonoperative treatment as the primary modality in patients with moderate to severe myelopathy. Low. Strong. If there is a role for nonoperative treatment as a primary treatment modality, it may be in the patient with mild myelopathy. However, it is not clear which specific forms of nonoperative treatment provide any benefit compared with the natural history. If nonoperative treatment is selected, we suggest care be taken to observe for neurological deterioration. Low. Weak. In those with asymptomatic spondylotic cord compression but no clinical myelopathy, the available literature neither supports nor refutes the notion that minor trauma is a risk factor for neurological deterioration. We suggest that patients should be counseled about this uncertainty. Low. Weak. Recommendation 4: In those with a clinical diagnosis of cervical spondylotic myelopathy but no ossification of the posterior longitudinal ligament, the available studies did not specifically address the issue of neurological deterioration secondary to minor trauma. However, in those with underlying ossification of the posterior longitudinal ligament, trauma may be more likely to cause worsening of existing myelopathy or even initiate symptoms in those who were previously asymptomatic. We suggest that patients should be counseled about these possibilities. Low. Weak.
This study is a combination of narrative and systematic review. Clinicians who deal with cervical... more This study is a combination of narrative and systematic review. Clinicians who deal with cervical spondylotic myelopathy (CSM) should be up-to-date with the emerging knowledge related to the cascade of pathobiological secondary events that take place under chronic cervical spinal cord compression. Moreover, by performing a systematic review, we aim to (1) describe the natural history and (2) determine potential risk factors that affect the progression of CSM. The pathophysiology, natural history, as well as the factors associated with clinical deterioration have not been fully described in CSM. For the first part of the study, a literature review was performed. To answer key questions 1 and 2 of the second goal, a systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 7, 2012. We included all articles that described the progression and outcomes of CSM for which no surgical intervention was given. By performing a narrative literature review, we found that the assumption that acute traumatic spinal cord injury and CSM share a similar series of cellular and molecular secondary injury events was made in the past. However, recent advances in basic research have shown that the chronic mechanical compression results in secondary injury mechanisms that have distinct characteristics regarding the nature and the temporal profile compared with those of spinal cord injury. For the purpose of the systematic review, 10 studies yielding 16 publications met inclusion criteria for key questions 2 and 3. Moderate-strength evidence related to the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Finally, there is low-strength evidence indicating that the area of circumferential compression is associated with deteriorating neurological symptoms. CSM has unique pathobiological mechanisms that mainly remain unexplored. Although the natural history of CSM can be mixed, surgical intervention eliminates the chances of the neurological deterioration. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: Evidence concerning the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Therefore, we recommend that patients with mild CSM be counseled regarding the natural history of CSM and have the option of surgical decompression explained. Moderate. Strong. SUMMARY STATEMENTS: Chronic compression of the spinal cord results in progressive neural cell loss related to secondary mechanisms including apoptosis, neuroinflammation, and vascular disruption.
An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To... more An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo. Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair. Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow-derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs. NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse. We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.
Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabol... more Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators. Chondrocytes from nine non-osteoarthritic patients and from six osteoarthritic (OA) donors at the time of total knee arthroplasty were chondro-differentiated in pellets for 2 weeks. Non-OA pellets were exposed for 72 hours to IL-1β/TNF-α and then cultured up to 14 days in 2 % FBS-supplemented NCCM or 2 % FBS-supplemented medium (control (ctr)). OA pellets were cultured in NCCM or ctr medium without ...
Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerativ... more Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.
The Journal of the Canadian Chiropractic Association, 2014
Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, o... more Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD's contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes.
Non-chondrodystrophic dog notochord cell conditioned medium was used to evaluate chondrocyte prot... more Non-chondrodystrophic dog notochord cell conditioned medium was used to evaluate chondrocyte proteoglycan production and cell proliferation. To evaluate the responsiveness of bovine disc-derived chondrocytes to notochord-cell conditioned medium with respect to proteoglycan and cell proliferation. In addition, to examine phenotypic changes of notochord cells cultured in monolayered as compared to 3-dimensional culture. Non-chondrodystrophic dogs maintain their intervertebral disc notochord cells into adulthood and are protected from having degenerative disc disease develop. The chondrodystrophic breeds such as beagles do not preserve these cells and have disc disease develop much earlier in life. The role of the notochord cell within the disc nucleus is poorly understood. Canine notochord cells were cultured within alginate beads in serum-deficient conditions using Dulbecco modified Eagle medium to produce notochord cell conditioned medium (NCCM). NCCM was used to stimulate bovine disc chondrocytes from which we evaluated proteoglycan production and cell proliferation as compared to chondrocytes grown in DMEM alone. In addition, parallel cultures of notochord cells were seeded within alginate beads as well as in monolayer and cultured in order to examine for differences in phenotype between the 2 culture conditions. The morphologic aspects of the intervertebral disc between the species differed markedly. A dose- dependent relationship was seen between proteoglycan production and NCCM concentration across various concentrations of NCCM in repeated experiments. Although there was a 4-fold increase in cell proliferation under all NCCM concentrations, this increase in cell proliferation was not dose dependent in the concentrations tested. Unlike chondrocytes, notochord cells do not adhere to tissue culture plate (monolayer) until at least day 4-6, do not markedly alter their phenotype, and rapidly assume masses of cells while floating within tissue culture medium. The biology of the disc-derived chondrocyte is profoundly affected by NCCM in that various concentrations of NCCM activate proteoglycan production in a dose-dependent fashion. However, in the doses tested in our study, cell proliferation was increased but in a nondose-dependent fashion. Notochord cells retain their phenotype even in monolayer and through the development of floating intimately associated masses of cells suggest the development and maintenance of cell-cell interaction. These masses of cells are retained even after 6 days in culture when they do attach to the tissue plate surface. The persistence of notochord cells in non-chondrodystrophic dog species suggests that these in vitro studies may mirror the milieu of the disc in vivo, in which the notochord cell may play a key role in disc homeostasis.
Systematic review. We sought to answer the following clinical questions: (1) Is structured exerci... more Systematic review. We sought to answer the following clinical questions: (1) Is structured exercise more effective in the treatment of chronic low back pain (LBP) than spinal manipulative therapy (SMT)? (2) Is structured exercise more effective in the treatment of chronic LBP than acupuncture? (3) Is SMT more effective in the treatment of chronic LBP than acupuncture? (4) Do certain subgroups respond more favorably to specific treatments? (5) Are any of these treatments more cost-effective than the others? Exercise, SMT, and acupuncture are widely used interventions in the treatment of chronic LBP. There is evidence that all of these approaches may offer some benefit for patients with chronic LBP when compared with usual care or no treatment. The relative benefits or cost-effectiveness of any one of these treatments when compared with the others are less well-defined, and it is difficult to identify specific subgroups of those with chronic LBP who may preferentially respond to a particular treatment modality. A systematic review of the literature was performed to identify randomized controlled trials comparing a structured exercise program, SMT, or acupuncture with one another in patients with chronic LBP. Two studies were identified comparing the use of structured exercise with SMT that met our inclusion criteria. Although these studies utilized different approaches for the exercise and SMT treatment groups, patients in both groups improved in terms of pain and function in both studies. Using random-effects modeling, there was no difference between the exercise and SMT groups when the data from these studies were pooled. We identified no studies meeting our inclusion criteria that compared acupuncture with either structured exercise or SMT or that addressed the relative cost-effectiveness of these approaches in the treatment of patients with chronic LBP. The studies identified indicate that structured exercise and SMT appear to offer equivalent benefits in terms of pain and functional improvement for those with chronic LBP with clinical benefits evident within 8 weeks of care. However, the level of evidence is low. There is insufficient evidence to comment on the relative benefit of acupuncture compared with either structured exercise or SMT or to address the differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is also insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP. Structured exercise and SMT appear to offer equivalent benefits in the management of pain and function for patients with nonspecific chronic LBP. If no clinical benefit is appreciated after using one of these approaches for 8 weeks, then the treatment plan should be reevaluated and consideration should be given to modifying the treatment approach or using alternate forms of care. Strength of recommendation: Weak.There is insufficient evidence regarding the relative benefits of the acupuncture compared with either structured exercise or SMT in the treatment of chronic LBP.There is insufficient evidence to address differential effects of structured exercise, SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There is insufficient evidence regarding the relative cost-effectiveness of structured exercise, SMT, or acupuncture in the treatment of chronic LBP.
Systematic review. To conduct a systematic review investigating the evidence of (1) efficacy, eff... more Systematic review. To conduct a systematic review investigating the evidence of (1) efficacy, effectiveness, and safety of nonoperative treatment of patients with cervical myelopathy; (2) whether the severity of myelopathy affects outcomes of nonoperative treatment; and (3) whether specific activities or minor injuries are associated with neurological deterioration in patients with myelopathy or asymptomatic stenosis being treated nonoperatively. Little is known about the appropriate role of nonoperative treatment in the management of cervical myelopathy, which is typically considered a surgical disorder. A systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 20, 2012. We included all articles that compared nonoperative treatments or observation with surgery for patients with cervical myelopathy or asymptomatic cervical cord compression to determine their effects on clinical outcomes, including myelopathy scales (Japanese Orthopaedic Association, Nurick), general health scores (36-Item Short Form Health Survey), and pain (neck and arm). Nonoperative treatments included physical therapy, medications, injections, orthoses, and traction. We also searched for articles evaluating the effect of specific activities or minor trauma in neurological outcomes. Case reports and studies with less than 10 patients in the exposure group were excluded. Of 54 citations identified from our search, 5 studies reported in 6 articles met inclusion criteria. In 1 randomized controlled study, there was low evidence that nonoperative treatment may yield equivalent or better outcomes than surgery in those with mild myelopathy. For moderate to severe myelopathy, nonoperative treatment had inferior outcomes versus surgery in 2 cohort studies, despite the fact that surgically treated patients were worse at baseline. There was insufficient evidence to determine whether specific activities or minor trauma is a risk factor for neurological deterioration in those with myelopathy or asymptomatic cord compression. There is a paucity of evidence for nonoperative treatment of cervical myelopathy, and further studies are needed to determine its role more definitively. In particular, for the patient with milder degrees of myelopathy, randomized studies comparing nonoperative with surgical treatment would be particularly helpful, as would trials comparing specific types of nonoperative treatments with the natural history of myelopathy. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: Because myelopathy is known to be a typically progressive disorder and there is little evidence that nonoperative treatment halts or reverses its progression, we recommend not routinely prescribing nonoperative treatment as the primary modality in patients with moderate to severe myelopathy. Low. Strong. If there is a role for nonoperative treatment as a primary treatment modality, it may be in the patient with mild myelopathy. However, it is not clear which specific forms of nonoperative treatment provide any benefit compared with the natural history. If nonoperative treatment is selected, we suggest care be taken to observe for neurological deterioration. Low. Weak. In those with asymptomatic spondylotic cord compression but no clinical myelopathy, the available literature neither supports nor refutes the notion that minor trauma is a risk factor for neurological deterioration. We suggest that patients should be counseled about this uncertainty. Low. Weak. Recommendation 4: In those with a clinical diagnosis of cervical spondylotic myelopathy but no ossification of the posterior longitudinal ligament, the available studies did not specifically address the issue of neurological deterioration secondary to minor trauma. However, in those with underlying ossification of the posterior longitudinal ligament, trauma may be more likely to cause worsening of existing myelopathy or even initiate symptoms in those who were previously asymptomatic. We suggest that patients should be counseled about these possibilities. Low. Weak.
This study is a combination of narrative and systematic review. Clinicians who deal with cervical... more This study is a combination of narrative and systematic review. Clinicians who deal with cervical spondylotic myelopathy (CSM) should be up-to-date with the emerging knowledge related to the cascade of pathobiological secondary events that take place under chronic cervical spinal cord compression. Moreover, by performing a systematic review, we aim to (1) describe the natural history and (2) determine potential risk factors that affect the progression of CSM. The pathophysiology, natural history, as well as the factors associated with clinical deterioration have not been fully described in CSM. For the first part of the study, a literature review was performed. To answer key questions 1 and 2 of the second goal, a systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 7, 2012. We included all articles that described the progression and outcomes of CSM for which no surgical intervention was given. By performing a narrative literature review, we found that the assumption that acute traumatic spinal cord injury and CSM share a similar series of cellular and molecular secondary injury events was made in the past. However, recent advances in basic research have shown that the chronic mechanical compression results in secondary injury mechanisms that have distinct characteristics regarding the nature and the temporal profile compared with those of spinal cord injury. For the purpose of the systematic review, 10 studies yielding 16 publications met inclusion criteria for key questions 2 and 3. Moderate-strength evidence related to the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Finally, there is low-strength evidence indicating that the area of circumferential compression is associated with deteriorating neurological symptoms. CSM has unique pathobiological mechanisms that mainly remain unexplored. Although the natural history of CSM can be mixed, surgical intervention eliminates the chances of the neurological deterioration. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: Evidence concerning the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Therefore, we recommend that patients with mild CSM be counseled regarding the natural history of CSM and have the option of surgical decompression explained. Moderate. Strong. SUMMARY STATEMENTS: Chronic compression of the spinal cord results in progressive neural cell loss related to secondary mechanisms including apoptosis, neuroinflammation, and vascular disruption.
An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To... more An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo. Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair. Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow-derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs. NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse. We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.
Uploads
Papers by W. Erwin