Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias.

A total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall-mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source-to-axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.

Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses.

BACKGROUND: Recent studies have demonstrated numerous biological properties of mesenchymal stem cells and their potential application in treating complex diseases or injuries to tissues that have difficulty regenerating, such as those affecting the central and peripheral nervous system. Thus, therapies that use mesenchymal stem cells are promising because of their high capacity for self-regeneration, their low immunogenicity, and their paracrine, anti-inflammatory, immunomodulatory, anti-apoptotic and neuroprotective effects. In this context, the purpose of this study was to evaluate the feasibility and safety of intrathecal transplantation of bone marrow-derived mesenchymal stem cells in horses, for future application in the treatment of neurological diseases. RESULTS: During the neurological evaluations, no clinical signs were observed that were related to brain and/or spinal cord injury of the animals from the control group or the treated group. The hematological and cerebrospinal fluid results from day 1 and day 6 showed no significant differences (P > 0.05) between the treated group and the control group. Additionally, analysis of the expression of matrix metalloproteinase (MMP) -2 and -9 in the cerebrospinal fluid revealed only the presence of pro-MMP-2 (latent), with no significant difference (P > 0.05) between the studied groups. CONCLUSIONS: The results of the present study support the hypothesis of the feasibility and safety of intrathecal transplantation of autologous bone marrow-derived mesenchymal stem cells, indicating that it is a promising pathway for cell delivery for the treatment of neurological disorders in horses.

Effect of pomegranate peel with/without autologous bone marrow on healing of acute cutaneous wounds in alloxan-induced diabetic rabbits.

Background: Healing of bum wounds is commonly associated with many complications. Every year various new repair materials are developed and experimentally used for treating burn wounds. Humans with diabetes mellitus usually suffer from chronic wound healing. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. One underlying factor that accompanies all diabetic ulcerations is poor vascular flow, a circumstance that impedes proper wound healing. Numerous studies have highlighted the importance of adequate vascular sufficiency and vessel proliferation in tissue repair and the lack thereof in diabetic wound healing. Other studies have looked at whether disarrayed capillary remodeling and maturation of vessels might play a role in impaired diabetic wound healing. Aim: This investigation has been planned to report the influence of treatment with a mixture of both the powder of pomegranate peel (PP) accompanied with an autologous bone marrow (BM) on the cure of burn injuries in experimentally induced diabetic rabbits. Methods: Alloxan monohydrate has been applied to create diabetes in 50 rabbits. Then in each rabbit, two deep second-degree burn wounds were experimentally created. The animals were then divided randomly into 5 treatment sections: non-treatment controls (C1), treated with an available commercial powder for wound (C2), treatment with powder of PP, treatment with alone BM, and the final group treated with PP powder with bone marrow (PPBM). The speed of wound closure and the histopathological changes during healing were measured. The levels of the biomarkers of rabbit platelet-derived growth factor AA (PDGF-AA) and rabbit protease-activated receptor 1 (PAR-1) were measured on days 0, 4, 8, and 12. Results: Wound healing was markedly more rapid in all the treatment groups versus the control non-treated group. Interestingly, a rapid wound cure was significantly observed in the PPBM group versus the other treatment ones. The histological assessment clarified a significant elevation in the fibroblast and collagen scores in the PPBM group versus the other sections. In addition, there were significant increases in the serum levels of the biomarkers PDGF-AA and PAR-1 among groups. Conclusion: Dependent on the results of current research, it can be concluded that both PP powder with BM PPBM significantly accelerate the healing process of burn wounds in experimentally induced diabetic rabbits.

Safety of autologous bone marrow stromal cell transplantation in dogs with acute spinal cord injury.

OBJECTIVE: To assess the feasibility and safety of transplantation of autologous bone marrow stromal cell (BMSC) in dogs with acute spinal cord injury (SCI). STUDY DESIGN: An open-label single-arm trial. ANIMALS: Dogs (n = 7) with severe SCI from T6 to L5, caused by vertebral fracture and luxation. METHODS: Decompressive and stabilization surgery was performed on dogs with severe SCI caused by vertebral fracture and luxation. Autologous BMSCs were obtained from each dog's femur, cultured, and then injected into the lesion in the acute stage. Adverse events and motor and sensory function were observed for >1 year after SCI. RESULTS: Follow-up was 29-62 months after SCI. No complications (eg, infection, neuropathic pain, worsening of neurologic function) were observed. Two dogs walked without support, but none of the 7 dogs had any change in sensory function. CONCLUSIONS: Autologous BMSC transplantation is feasible and safe in dogs with acute SCI. Further studies are needed to determine the efficacy of this therapy.

Heterotopic implantation of autologous bone marrow in rock pigeons (Columba livia): possible applications in avian bone grafting.

Autologous bone marrow, alone or as a composite marrow graft, has received much attention in various species. To assess the potential osteogenicity of autologous, extramedullary bone marrow implants in an avian model, 24 adult pigeons (Columba livia) were given intramuscular implantations of autologous marrow aspirated from the medial tibiotarsus. Birds were euthanatized at 1, 4, 6, 8, 10, and 12 weeks after surgery to evaluate whether ectopic bone had formed at the implant sites. Primary evaluations by in situ radiography and postmortem histologic examinations showed no evidence of bone formation. Further evaluation with histologic scores and histomorphometry revealed a significantly increased rate of angiogenesis at the implant sites by the sixth and tenth week postimplantation (P < .05). No significant differences between the treatment and control sites were present at any other endpoints. Results of this study show that, although autologous bone marrow lacks heterotopic osteogenic potentials in this avian model, it could still function as a useful adjunct to routine bone grafting techniques because of its unique capabilities to promote early angiogenesis.

Migration and differentiation of canine bone marrow stromal cells transplanted into the developing mouse brain.

To evaluate whether canine bone marrow stromal cells (BMSCs) can migrate and adopt neural phenotypes in the developing mouse brain we transplanted fluorescently labeled BMSCs into the lateral ventricle of immunocompromised neonatal mice. Most fibroblasts, used as a control, and BMSCs isolated from adult dogs remained around the injection site and exhibited a spindle-shaped appearance. A small number of BMSCs from young dogs were found in the subventricular zone, rostral migratory stream, and olfactory bulbs, and retained expression of neuron marker. Our findings suggest that BMSCs isolated from adult dogs have limited ability of migration and differentiation toward neural cells in the developing brain. Bone marrow of young dogs may contain a primitive stem cell population with neural differentiation capacity.

Developments and translational relevance for the canine haematopoietic cell transplantation preclinical model.

The development of safe and reliable haematopoietic cell transplantation (HCT) protocols to treat human patients with malignant and non-malignant blood disorders was highly influenced by preclinical studies obtained in random-bred canines. The surmounted barriers included recognizing the crucial importance of histocompatibility matching, establishing long-term donor haematopoietic cell engraftment, preventing graft-vs-host disease and advancing effective conditioning and post-grafting immunosuppression protocols, all of which were evaluated in canines. Recent studies have applied the tolerance inducing potential of HCT to solid organ and vascularized composite tissue transplantation. Several advances in HCT and tolerance induction that were first developed in the canine preclinical model and subsequently applied to human patients are now being recruited into veterinary practice for the treatment of malignant and non-malignant disorders in companion dogs. Here, we review recent HCT advancements attained in the canine model during the past 15 years.

Efficacy of autologous bone marrow mononuclear cell transplantation in dogs with chronic spinal cord injury.

Background: Spinal cord injury (SCI) is relatively common in dogs and is a devastating condition involving loss of sensory neurons and motor neurons. However, the main clinical protocol for the management of SCI is surgery to decompress and stabilize the vertebra. Cell transplantation therapy is a very promising strategy for the treatment of chronic SCI, but extensive preclinical and clinical research work remains. Aim: The aim of this study is to confirm the effect of bone marrow-derived mononuclear cell (BM-MNC) transplantation for chronic SCI in dogs. Methods: We tested the treatment efficiency of chronic SCI in 12 dogs using BM-MNC transplantation. Neurological evaluation used the Texas Spinal Cord Injury Scale (TSCIS). Concurrently, we characterized the transplanted cells by evaluation using quantitative real-time polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Result: All dogs had a pre-transplantation TSCIS score of 0. Two animals did not show any improvement in their final TSCIS scores. The remaining 10 dogs (83.4%) achieved improvement in the final TSCIS scores. Five of them (41.7%) regained ambulatory function with a TSCIS score greater than 10. We determined that canine BM-MNCs expressed hepatocyte growth factor (HGF) mRNA at higher levels than other cytokines, with significant increases in HGF levels in cerebrospinal fluid within 48 hours after autologous BM-MNC transplantation into the subarachnoid space of the spinal dura matter in dogs. Conclusions: BM-MNC transplantation may be effective for at least some cases of chronic SCI.

Histology and immunohistochemistry study of ovine tendon grafted with cBMSCs and BMMNCs after collagenase-induced tendinitis.

OBJECTIVES: The aim of this study was to compare the regeneration abilities of cultured bone marrow mesenchymal cells (cBMSC) and bone marrow mononuclear cells (BMMNC) with fibrin glue, saline solution and sham control in collagenase-induced tendinitis of the Achilles tendon in sheep. METHODS: Six sheep were recruited randomly to each group: cBMSC, BMMNC, fibrin, saline and sham control. Each group received the relative treatment two weeks after inducing lesions (T(0)). After eight weeks (T(8)) of treatment, the tendons were harvested and evaluated for histomorphology, Collagen type I, III, Cartilage Oligomeric Matrix Protein (COMP) and CD34 positive cells expression. RESULTS: Histology and immunohistochemistry showed similar capabilities of cBMSC and BMMNC to restore the architecture of fibres and Extra Cellular Matrix (ECM), with a high expression of collagen type I and COMP and a very low expression of collagen type III in treated tendons. The complete architectural disruption of fibres, dramatic reduction of collagen Type I and COMP expression and increase collagen type III expression were commonly observed in tendons treated with fibrin or saline only. The presence of CD34 positive cells was appreciable in the BMMNC group while few cBMSC showed this cluster of differentiation, not expressed in tendons treated with fibrin or saline. CLINICAL SIGNIFICANCE: The data in this study show the efficacy of cBMSC and BMMNC in regenerating tendon tissue after collagenase-induced tendinitis.

Supernumerary Incisors in CB6F1 Mice Conditioned with Chemotherapy and Total Body Irradiation before Bone Marrow Transplantation.

Multiple adult female CB6F1 mice presented with supernumerary incisors after preconditioning with chemotherapy and total body irradiation for bone marrow transplantation (BMT). Mice received nonmyeloablative total body irradiation (3 Gy) and either cyclophosphamide or bendamustine, followed by BMT and posttransplantation cyclophosphamide or bendamustine. Here we describe the clinical presentation, µCT findings, and histopathologic evaluation of the affected mice. These analyses confirmed the gross diagnosis and revealed details of the abnormal tooth morphology. We surmise that the combination of total body irradiation and chemotherapy resulted in the abnormal formation of supernumerary incisors. Supernumerary teeth should be considered as a potential confounding factor in tracking weight loss after BMT. These conditions can be managed to allow animals to reach their intended scientific endpoint.

Combination therapy of canine osteosarcoma with canine bone marrow stem cells, bone morphogenetic protein and carboplatin in an in vivo model.

Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The therapeutic protocols adopted for dogs and humans are very similar, involving surgical options such as amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. However, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treatments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined with recombinant human bone morphogenetic protein (rhBMP-2) may be associated with decreases of the tumorigenic potential of canine OSA. The aim of this study was to analyse the efficacy of chemotherapy with carboplatin and rhBMP-2 with MSCs in a canine OSA in vivo model. Canine OSA cells were implanted in mice Balb-c/nude with MSCs, rhBMP-2 and carboplatin. Flow cytometry and PCR for markers involved in tumour suppression pathways were analysed. Results showed that the combination of MSCs and rhBMP-2 reduced tumour mass and infiltration of neoplastic cells in tissues more efficiently than carboplatin alone. Thus it was demonstrated that the use of rhBMP-2 and MSCs, in combination with conventional antineoplastic, may be an efficient treatment strategy.

Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses.

It has been proven that mesenchymal stromal cells (MSCs) can differentiate into tenocytes. Attempts to repair tendon lesions have been performed, mainly using scaffold carriers in experimental settings. In this article, we describe the clinical use of undifferentiated MSCs in racehorses. Significant clinical recovery was achieved in 9 of 11 horses evaluated using ultrasound analysis and their ability to return to racing. Our results show that the suspension of a small number of undifferentiated MSCs may be sufficient to repair damaged tendons without the use of scaffold support. Ultrasound scanning showed that fibers were correctly oriented. By using undifferentiated cells, no ectopic bone deposition occurred. A sufficient number of cells was recovered for therapeutic purposes in all but 1 case. We suggest that the use of autologous MSCs is a safe therapeutic method for treating incompletely (i.e., not full-thickness) damaged tendons.

Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon.

Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons), AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received lactated Ringer's solution as control. Serial ultrasound assessment was performed prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks, histopathology and gene expression analyses were performed. At week 6, the ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier improvement, whilst all treatment groups reached the same level at week 10, which was superior to the control group. Collagen orientation scores on histological examination suggested a better outcome in treated tendons. Gene expression was indicative of better tissue regeneration after all treatments, especially for BM-MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial effect was elicited by all treatments compared with the control group. Although differences between treatments were relatively small, BM-MSCs resulted in a better outcome than PRP and AT-MSCs.

A combination chemotherapy protocol with dose intensification and autologous bone marrow transplant (VELCAP-HDC) for canine lymphoma.

Twenty-eight dogs with lymphoma were treated with a 12-week, 5-drug chemotherapy protocol concluding with high-dose cyclophosphamide supported by autologous bone marrow transplants. A dose escalation design was used to determine the maximum tolerated cyclophosphamide dose (MTD) in this setting. Three cyclophosphamide dose levels were given: 300 mg/ m2 IV (groupl, 3 dogs), 400 mg/m2 IV (group 2, 12 dogs), and 500 mg/m2 IV (group 3, 13 dogs); and the MTD was 500 mg/m2 IV. Toxicity was common but mild, and the dose-limiting toxicity was myelosuppression, specifically neutropenia. No dog died as a result of treatment-related toxicity. One dog in group 3 developed fever, neutropenia, and presumed sepsis and responded promptly to routine management. No other dog required hospitalization. Lower stage and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3]) compared with the lower doses combined (groups 1 and 2) were significantly associated with longer remission duration (all P < .0001). Median remission duration for dogs in group 3 was 54 weeks, compared with 21 weeks for dogs in groups 1 and 2 combined. Factors associated with longer survival time were lower stage (P = .042) and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3] compared with the lower doses combined [groups 1 and 2]) (P = .027). Median survival time for dogs in group 3 was 139 weeks, compared with 43 weeks and 68 weeks for dogs in groups 1 and 2, respectively.

Autologous bone marrow aspirate for treatment of superficial digital flexor tendonitis in 105 racehorses.

To evaluate a treatment protocol whereby superficial digital flexor (SDF) tendonitis in Thoroughbred and Standardbred racehorses was treated with autologous bone marrow aspirate (ABMA) obtained from the sternebrae. This treatment was combined with desmotomy of the accessory ligament of the SDF tendon (DAL-SDFT) in selected cases. Medical records of 105 horses treated using the reported protocol were reviewed. Signalment, history and details of treatment were recorded. Racing records were reviewed and performance recorded. Of Thoroughbreds, 82 per cent had one or more starts within the follow-up period and 59 per cent had five or more starts. Of Standardbreds, 76 per cent had one or more starts and 62 per cent had five or more starts. A statistically significant difference was found when comparing race starts between sexes, with females having less starts than males (≥1start P=0.017 and ≥5 starts P=0.008, respectively). The proportions of horses having one or more starts and five or more starts did not differ significantly if a DAL-SDFT was performed or not (P=0.31 and 0.63, respectively). Horses with a core lesion in the body of the SDFT have a good prognosis for return to racing following intralesional ABMA injection. Addition of DAL-SDFT to the treatment regimen did not significantly influence outcome.

Assessment of regeneration in meniscal lesions by use of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans.

Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study.

Squamous cell carcinomas (SCC) of the upper aero-digestive tract are characterized by a high incidence of bone invasion; their treatment often requires large and damaging surgical resections and radiotherapy. Surgical and radiotherapeutic procedures generate irreversible effects on normal tissues, involving injuries on their reparation properties, especially on bone. The quality of life of patients undergoing major surgery and radiotherapy in maxillary and mandible areas is often reduced but could be improved by bone reconstructions. Bone reconstructions are rarely performed because surgery is complex and unsafe in irradiated bone. The aim of the study was to evaluate the bone reconstruction possibilities of macroporous biphasic calcium phosphate (MBCP) associated to autologous bone marrow (BM) graft injected after irradiation. MBCP hollowed blocks were specially designed and implanted in tibia and femur bone before irradiation in a dog model. Implants were removed after 18 weeks. This is the first report of experiments performed after radiation delivery using high fractionated doses approximating usual treatment of SCC in human. The quality of the bone adjacent to implanted MBCP and the bone ingrowth's rates were evaluated. The qualitative and quantitative role of BM grafts associated with the MBCP implants was determined, using scanning electron microscopy linked to quantitative image analysis. A direct contact between newly formed bone and MBCP implants associated to BM graft was observed, without fibrous interposition. The new-bone formation was statistically increased inside the MBCP (P=0.0126) by BM grafts. This study demonstrates that BM graft added to MBCP constitute an appropriate material to be considered in case of bone defect occurring in irradiated tissue, and could be foreseen for use after bone removal for oncologic obligations.

Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.

We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).

Functional and regenerative effects of local administration of autologous mononuclear bone marrow cells combined with silicone conduit on transected femoral nerve of rabbits.

The inoculation of cells into injury sites can accelerate and improve the quality of nerve regeneration. This study aimed to evaluate the functional and regenerative effects of mononuclear autologous bone marrow cells (MABMC) combined with silicon conduit grafting in rabbit femoral nerves. Twenty-eight animals were allocated to one of two groups: treatment group (TG) or control group (CG), divided according to the time of evaluation, at either 50 or 75 days. After neurotmesis of the femoral nerve, surgical repair was performed with nerve autografts in silicon conduits, leaving a 5mm gap in both groups. The TG received MABMC in silicon conduits, and CG received a sham saline inoculum. Histological, clinical and electrophysiological analyses detected no differences between groups, but analysis of leg diameter showed that TG diameters were larger. This cell therapy did not improve regeneration of the femoral nerve, but there was a tendency for better functional recovery.