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Journal of Neurorestoratology  2018, Vol. 6 Issue (1): 136-145    doi: 10.26599/JNR.2018.9040011
Research Article     
Local immunomodulation and muscle progenitor cells induce recovery in atrophied muscles in spinal cord injury patients
Gustavo A. Moviglia(✉), M. Teresita Moviglia Brandolino, Damián Couto, Samanta Piccone
Centre for Tissue Engineering and Cellular Therapy Research (CIITT), Universidad Maimonides, Buenos Aires C1405BCK, Argentina
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Abstract  Objectives:

Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.

Setting:

Out Patient Treatment, Universidad Maimonides, Buenos Aires, Argentina.

Methods:

After receiving spinal cord cell therapy and intensive rehabilitation, 7 chronic complete spinal cord injury (SCI) patients (4 people with paraplegia and 3 people with quadriplegia) regained muscular electrical activity in previously denervated territories. However, signs of severe muscular atrophy persisted. Looking to reverse chronic muscular atrophy, atrophied muscles with electrical activity were implanted with autologous type 1 macrophages (Mo1) and autologous tissue-specific T helper 1 Cells (Th1) associated with autologous muscular progenitor cells (MPC). The Mo1 and Th1 used cells were named Effector Cells (EC). Each muscle received between 6 to 8 implants, one every 6 weeks. Cellular therapy was combined with intensive rehabilitation program.

Results:

Sonogram and histological signs of recovery started eight weeks after the first implant. Sonograms showed progressively muscle volume increasing and gradually replacement of hyperechogenic muscle tissue by hypoechogenic muscle bands (resembling normal muscular structure). New bands were distributed parallel to the main muscle axis, along the entire muscular length. Histological samples of hypoechogenic bands showed new and normal muscular tissue. Changes were seen in 7/7 patients. Non-significant side events were detected in any patient over the 24 months of follow up.

Conclusions:

The results presented here suggest that the combination of immune and regenerative cell therapy may play an important therapeutic role in clinical and histological recovery of chronic muscular atrophy.



Key wordsimmunomodulation      chronic muscular atrophy      muscular progenitor cells      spinal cord injury     
Received: 18 September 2018      Published: 30 December 2018
Corresponding Authors: Gustavo A. Moviglia   
Cite this article:

Gustavo A. Moviglia, M. Teresita Moviglia Brandolino, Damián Couto, Samanta Piccone. Local immunomodulation and muscle progenitor cells induce recovery in atrophied muscles in spinal cord injury patients. Journal of Neurorestoratology, 2018, 6: 136-145.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2018.9040011     OR     http://jnr.tsinghuajournals.com/Y2018/V6/I1/136

Fig. 1Quadriceps evaluation patient #7: (A, B) needle electromyography activity in a flaccid muscle without muscular contraction; (C) ultrasound that shows signs of severe atrophy (*) transversal measure of the muscle 1.1 cm of thickness is observed; (D) muscle biopsy with signs of severe muscular atrophy, fat infiltration and fibrosis.
#SexAge in yearsTime since injury until treatmentInjury levelASIAClinic featuresMuscles that recovered electric activity after spinal cord cell treatment
1M237 yearsC 5ASpastic quadriplegiaTriceps Paraspinals Abdominals (rectus, obliques, transverse) Gluteus Quadriceps psoas
2M3014 yearsC 6ASpastic quadriplegiaTriceps Paraspinals Abdominals (rectus, obliques, transverse) Gluteus Anal Sphincter
3M273 yearsT 4ASpastic paraplegiaPsoas Adductors Quadriceps Hamstrings Gluteus
4F183 yearsT 12AFlaccid paraplegiaPsoas Adductors Quadriceps Hamstrings
5M236 yearsT 4AFlaccid paraplegiaAbdominals (rectus, obliques, transverse) Paraspinals Psoas Quadriceps Hamstring Adductors Tibialis anterior Triceps sural gluteus
6F538 yearsT 4AFlaccid paraplegiaAbdominals (rectus, obliques, transverse) Paraspinals Psoas Gluteus. Anal sphincter
7F2712 yearsT 12AFlaccid paraplegiaPsoas Adductors Quadriceps Hamstrings Triceps sural Tibialis anterior Gluteus Anal sphincter
Table 1Pre-treatment clinical features of the previous SCI treated patients.
Fig. 2Ultrasound and histology, pre and post implant. (A) The bracket indicates the white muscle band that indicates fibro-adipose atrophy as is corroborated for the muscle biopsy as is shows in B picture. (C) Picture indicates the poor but existing neuromuscular end plates (brown spots) through the Synaptophysin IHC stain. (D) After the MPC treatment there is able to see the triple muscle bands detected by sonography: outer black band indicates normal muscle tissue, as is corroborated by the histology image shows in Picture E. Middle gray band indicates neo tissue muscle growth as is corroborated by the histology image of picture F. Picture G shows that the neuromuscular end plates have increased in number and extension after the MPC treatment. The inner white muscle band seen in picture D is not marked by brackets neither a histology control showed.
GroupMusclesNumber of cells implanted in each muscle (EC+MPC)
Small musclesDeltoid, supraspinous, mayor and minor pectoral, supinator, finger extensors, hand muscles.5×106
Medium musclesTriceps, Biceps, Abdominals (rectus, obliquus), spinals, adductors, tibialis, gastrocnemius10×106
Large musclesPsoas, quadriceps, gluteus, hamstrings15×106
Table 2Number of cells implanted depending on muscle characteristics
Signs/symptomsN° patients affectedobservations
Flu like syndrome2/7In all cases they did not last more than 72 h after the implant
Local events at the implant site: hematoma, edema, skin symptoms (burning, pain)6/7Local hematoma was the most common sign.
Muscular enzyme modification (phosphokinase, aldolasa) 7 days after implant.0/7
Blood, lung, heart, kidney function affected0/7Measured by clinical and laboratory tests
Table 3Frequency of side effects associated to the implant.
#Injury levelImplanted musclesKendall scoreFunctional changes
Before treatmentAfter treatment 18 months (6 to 8 implants in each muscle)
RightleftRightleft
1C 5Triceps0/50/52/52/5Independent standing with AFO and one support. Independent walking with AFO and walker. Independent seating without back support.
Abdominals (rectus, obliques, transverse)0/50/52/52/5
Spinals (T1 to L5)0/50/52/52/5
Gluteus0/50/51/51/5
Psoas0/50/51/51/5
Quadriceps0/50/51/51/5
2C 6Triceps1/51/53/53/5Independent standing with AFO and 2 supports. Independent seating without back support.
Abdominals (rectus, obliques, transverse)0/50/52/52/5
Spinals0/50/52/52/5
Gluteus0/50/50/50/5
Psoas0/50/50/50/5
Anal sphincter0Strong Voluntary contraction
3T 4Abdominals (rectus, obliques, transverse)0/50/53/53/5Independent standing with AFO and walker. Seating position without back support.
Spinals0/50/53/53/5
Gluteus0/50/51/51/5
4T 12Psoas0/50/52/52/5Independent standing with AFO and one support. Independent walking with AFO and walker.
Quadriceps0/50/51/51/5
Adductors0/50/52/52/5
Hamstrings0/50/51/51/5
Gluteus0/50/50/50/5
5T 4Abdominals (rectus, obliques, transverse)0/50/51/51/5Independent standing with AFO and two supports. Independent walking with AFO and walker.
Paraspinals0/50/51/51/5
Psoas0/50/51/51/5
Quadriceps0/50/50/50/5
Adductors0/50/50/50/5
Tibialis anterior0/50/50/50/5
Triceps sural0/50/50/50/5
6T 4Abdominals (rectus, obliques, transverse)0/50/51/51/5Independent standing with AFO and two supports. Seating position without back support. Active movements of upper limbs without external trunk support.
Paraspinals0/50/51/51/5
Psoas0/50/50/50/5
Gluteus0/50/50/50/5
Anal sphincter00
7T 12Psoas0/50/52/52/5Independent standing with AFO and one support. Independent walking with AFO and cane.
Adductors0/50/52/52/5
Quadriceps0/50/51/51/5
Hamstrings0/50/52/52/5
Triceps sural0/50/51/51/5
Tibialis anterior0/50/50/50/5
Gluteus0/50/51/51/5
Anal sphincter0Poor voluntary contraction
Table 4Implanted muscles and clinical evolution.
Fig. 3Muscular biopsy controls: Actin HRP stain (A) pre-implant, (B) 4-month post-implant; desmin HRP stain (C) pre-implant, (D) 4-month post-implant; Myo D HRP stain (E) pre-implant, (F) 4-month post-implant; Myogenin HRP stain (G) pre-implant, (H) 4-month post-implant; collagen Type I HRP stain (I) pre-implant, (J) 4-month post-implant; collagen Type IV HRP Stain (K) pre-implant, (L) 4-month post-implant. White asterisk signs (*) the large muscle fibers. Yellow asterisk signs (*) new formed muscle fibers. Orange asterisk signs (*) the interstitial muscular progenitor cells.
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