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BMC Neurology

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Open Access 01-12-2023 | Central Nervous System Trauma | Research

The density of bone marrow mononuclear cells and CD34+ cells in patients with three neurologic conditions

Authors: Kien Trung Nguyen, Nhung Thi My Hoang, Hoang-Phuong Nguyen, Liem Nguyen Thanh

Published in: BMC Neurology | Issue 1/2023

Abstract

Background

This study aimed to identify the density of mononuclear cells (MNCs) and CD34+ cells in the bone marrow of patients with three neurologic conditions.

Methods

The study included 88 patients with three neurologic conditions: 40 with cerebral palsy (CP) due to oxygen deprivation (OD), 23 with CP related to neonatal icterus (NI), and 25 with neurological sequelae after traumatic brain injury. Bone marrow aspiration was conducted from the patients’ bilateral anterior iliac crest under general anesthesia in an operating theater. MNCs were isolated by Ficoll gradient centrifugation and then infused intrathecally.

Results

There was a significant difference in the average MNC per ml and percentage of CD34+ cells by the type of disease, age group, and infusion time (p value < 0.05). The multivariable regression model showed the percentage of CD34+ association with the outcome (gross motor function 88 items- GMFM-88) in patients with CP.

Conclusions

The density of MNCs was 5.22 million cells per mL and 5.03% CD34+ cells in patients with three neurologic conditions. The highest density of MNCs in each ml of bone marrow was found in patients with CP due to OD, whereas the percentage of CD34+ cells was the highest among patients with CP related to NI.

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Huang L, Wang G. The effects of different factors on the behavior of neural stem cells. Stem Cells Int. 2017;2017:9497325. https://doi.org/10.1155/2017/9497325.CrossRef

Gogel S, Gubernator M, Minger SL. Progress and prospects: stem cells and neurological diseases. Gene Ther. 2011;18(1):1–6. https://doi.org/10.1038/gt.2010.130.CrossRef

Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000;61(4):364–70. https://doi.org/10.1002/1097-4547(20000815)61:43.0.CO;2-C.

Liu X, Fu X, Dai G, Wang X, Zhang Z, Cheng H, et al. Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy. J Transl Med. 2017;15(1):48. https://doi.org/10.1186/s12967-017-1149-0.CrossRef

Song CG, Zhang YZ, Wu HN, Cao XL, Guo CJ, Li YQ, et al. Stem cells: a promising candidate to treat neurological disorders. Neural Regen Res. 2018;13(7):1294–304. https://doi.org/10.4103/1673-5374.235085.

Pan K, Deng L, Chen P, Peng Q, Pan J, Wu Y, et al. Safety and feasibility of repeated intrathecal allogeneic bone marrow-derived mesenchymal stromal cells in patients with neurological diseases. Stem Cells Int. 2019;2019:8421281. https://doi.org/10.1155/2019/8421281.CrossRef

Nguyen TL, Nguyen HP, Nguyen TK. The effects of bone marrow mononuclear cell transplantation on the quality of life of children with cerebral palsy. Health Qual Life Outcomes. 2018;16(1):164. https://doi.org/10.1186/s12955-018-0992-x.CrossRef

Cox CS Jr, Hetz RA, Liao GP, Aertker BM, Ewing-Cobbs L, Juranek J, et al. Treatment of severe adult traumatic brain injury using bone marrow mononuclear cells. Stem Cells. 2017;35(4):1065–79. https://doi.org/10.1002/stem.2538.CrossRef

Sharma AK, Sane HM, Kulkarni PP, Gokulchandran N, Biju H, Badhe PB. Autologous bone marrow mononuclear cell transplantation in patients with chronic traumatic brain injury- a clinical study. Cell Regen. 2020;9(1):3. https://doi.org/10.1186/s13619-020-00043-7.CrossRef

10.

Nguyen LT, Nguyen AT, Vu CD, Ngo DV, Bui AV. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial. BMC Pediatr. 2017;17(1):104. https://doi.org/10.1186/s12887-017-0859-z.CrossRef

11.

Longo M, Hankins GD. Defining cerebral palsy: pathogenesis, pathophysiology and new intervention. Minerva Ginecol. 2009;61(5):421–9.

12.

Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma. 2010;27(8):1529–40. https://doi.org/10.1089/neu.2010.1358.CrossRef

13.

Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M. Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Rep Transplant. 2012;2012:825289. https://doi.org/10.1155/2012/825289.CrossRef

14.

Wang X, Cheng H, Hua R, Yang J, Dai G, Zhang Z, et al. Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study. Cytotherapy. 2013;15(12):1549–62.CrossRef

15.

Sharma A, Sane H, Gokulchandran N, Kulkarni P, Gandhi S, Sundaram J, et al. A clinical study of autologous bone marrow mononuclear cells for cerebral palsy patients: a new frontier. Stem Cells Int. 2015;905874(10):18.

16.

Chen G, Wang Y, Xu Z, Fang F, Xu R, Hu X, et al. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy. J Transl Med. 2013;11(21):1479–5876.

17.

Bansal H, Singh L, Verma P, Agrawal A, Leon J, Sundell IB, et al. Administration of Autologous Bone Marrow-Derived Stem Cells for treatment of cerebral palsy patients: a proof of concept. J Stem Cells. 2016;11(1):37–49.

18.

Cox CS Jr, Baumgartner JE, Harting MT, Worth LL, Walker PA, Shah SK, et al. Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children. Neurosurgery. 2011;68(3):588–600. https://doi.org/10.1227/NEU.0b013e318207734c.CrossRef

19.

Tian C, Wang X, Wang X, Wang L, Wang X, Wu S, et al. Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain injury by lumbar puncture. Exp Clin Transplant. 2013;11(2):176–81. https://doi.org/10.6002/ect.2012.0053.CrossRef

20.

Sharma A, Sane H, Kulkarni P, Yadav J, Gokulchandran N, Biju H, et al. Cell therapy attempted as a novel approach for chronic traumatic brain injury - a pilot study. Springerplus. 2015;4:26. https://doi.org/10.1186/s40064-015-0794-0.CrossRef

21.

Xinquang. Stem cell therapy for traumatic brain injury: a progress update. Ann Neurol Surg. 2018;2(1):1008.

22.

Chang YS, Choi SJ, Ahn SY, Sung DK, Sung SI, Yoo HS, et al. Timing of umbilical cord blood derived mesenchymal stem cells transplantation determines therapeutic efficacy in the neonatal hyperoxic lung injury. PLoS One. 2013;8(1):e52419. https://doi.org/10.1371/journal.pone.0052419.CrossRef

23.

Corrigan JD, Smith-Knapp K, Granger CV. Validity of the functional independence measure for persons with traumatic brain injury. Arch Phys Med Rehabil. 1997;78(8):828–34. https://doi.org/10.1016/s0003-9993(97)90195-7.CrossRef

24.

Sharma A, Gokulchandran N, Chopra G, Kulkarni P, Lohia M, Badhe P, et al. Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Cell Transplant. 2012;21(Suppl 1):S79–90. https://doi.org/10.3727/096368912X633798.CrossRef

25.

Chen G, Wang Y, Xu Z, Fang F, Xu R, Wang Y, et al. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy. J Transl Med. 2013;11:21. https://doi.org/10.1186/1479-5876-11-21.CrossRef

26.

27.

Thanh LN, Trung KN, Duy CV, Van DN, Hoang PN, Phuong ANT, et al. Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial. BMC Pediatr. 2019;19(1):290. https://doi.org/10.1186/s12887-019-1669-2.CrossRef

28.

Dedeepiya VD, Rao YY, Jayakrishnan GA, Parthiban JK, Baskar S, Manjunath SR, et al. Index of CD34+ cells and mononuclear cells in the bone marrow of spinal cord injury patients of different age groups: a comparative analysis. Bone Marrow Res. 2012;2012:787414. https://doi.org/10.1155/2012/787414.CrossRef

29.

Liem NT, Chinh VD, Phuong DTM, Van Doan N, Forsyth NR, Heke M, et al. Outcomes of bone marrow-derived mononuclear cell transplantation for patients in persistent vegetative state after drowning: report of five cases. Front Pediatr. 2020;8:564. https://doi.org/10.3389/fped.2020.00564.CrossRef

30.

Liem NT, Huyen TL, Huong LT, Doan NV, Anh BV, Anh NTP, et al. Outcomes of bone marrow mononuclear cell transplantation for neurological sequelae due to intracranial hemorrhage incidence in the neonatal period: report of four cases. Front Pediatr. 2019;7:543. https://doi.org/10.3389/fped.2019.00543.CrossRef

31.

Chernykh ER, Shevela EY, Leplina OY, Tikhonova MA, Ostanin AA, Kulagin AD, et al. Characteristics of bone marrow cells under conditions of impaired innervation in patients with spinal trauma. Bull Exp Biol Med. 2006;141(1):117–20. https://doi.org/10.1007/s10517-006-0109-0.CrossRef

32.

Harting MT, Cox CS, Day MC, Walker P, Gee A, Brenneman MM, et al. Bone marrow-derived mononuclear cell populations in pediatric and adult patients. Cytotherapy. 2009;11(4):480–4. https://doi.org/10.1080/14653240902960452.CrossRef

33.

Mohamadnejad M, Namiri M, Bagheri M, Hashemi SM, Ghanaati H, Zare Mehrjardi N, et al. Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol. 2007;13(24):3359–63. https://doi.org/10.3748/wjg.v13.i24.3359.CrossRef

34.

Hernandez P, Cortina L, Artaza H, Pol N, Lam RM, Dorticos E, et al. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis. 2007;194(2):e52–6. https://doi.org/10.1016/j.atherosclerosis.2006.08.025.CrossRef

35.

Ema H, Suda T, Miura Y, Nakauchi H. Colony formation of clone-sorted human hematopoietic progenitors. Blood. 1990;75(10):1941–6.CrossRef

36.

Van E, Bender J, Lee W, Schilling M, Smith A, Smith S, et al. Harvesting, characterization, and culture of CD34+ cells from human bone marrow, peripheral blood, and cord blood. Blood Cells. 1994;20(2–3):411–23.

37.

Sutherland DR, Keating A, Nayar R, Anania S, Stewart AK. Sensitive detection and enumeration of CD34+ cells in peripheral and cord blood by flow cytometry. Exp Hematol. 1994;22(10):1003–10.

38.

Scott MA, Gordon MY. In search of the haemopoietic stem cell. Br J Haematol. 1995;90(4):738–43. https://doi.org/10.1111/j.1365-2141.1995.tb05190.x.CrossRef

39.

Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med. 1997;337(6):373–81. https://doi.org/10.1056/nejm199708073370602.CrossRef

40.

Fritsch G, Stimpfl M, Kurz M, Printz D, Buchinger P, Fischmeister G, et al. The composition of CD34 subpopulations differs between bone marrow, blood and cord blood. Bone Marrow Transplant. 1996;17(2):169–78.

41.

Bender JG, To LB, Williams S, Schwartzberg LS. Defining a therapeutic dose of peripheral blood stem cells. J Hematother. 1992;1(4):329–41. https://doi.org/10.1089/scd.1.1992.1.329.CrossRef

42.

Chen L, Huang H, Xi H, Xie Z, Liu R, Jiang Z, et al. Intracranial transplant of olfactory ensheathing cells in children and adolescents with cerebral palsy: a randomized controlled clinical trial. Cell Transplant. 2010;19(2):185–91. https://doi.org/10.3727/096368910X492652.CrossRef

43.

Mancias-Guerra C, Marroquin-Escamilla AR, Gonzalez-Llano O, Villarreal-Martinez L, Jaime-Perez JC, Garcia-Rodriguez F, et al. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy. 2014;16(6):810–20. https://doi.org/10.1016/j.jcyt.2014.01.008.CrossRef

44.

Zhang C, Huang L, Gu J, Zhou X. Therapy for cerebral palsy by human umbilical cord blood mesenchymal stem cells transplantation combined with basic rehabilitation treatment: a case report. Glob Pediatr Health. 2015;2:2333794X15574091. https://doi.org/10.1177/2333794X15574091.CrossRef

45.

He S, Luan Z, Qu S, Qiu X, Xin D, Jia W, et al. Ultrasound guided neural stem cell transplantation through the lateral ventricle for treatment of cerebral palsy in children. Neural Regen Res. 2012;7(32):2529–35. https://doi.org/10.3969/j.issn.1673-5374.2012.32.007.CrossRef

46.

Hong BY, Jo L, Kim JS, Lim SH, Bae JM. Factors influencing the gross motor outcome of intensive therapy in children with cerebral palsy and developmental delay. J Korean Med Sci. 2017;32(5):873–9. https://doi.org/10.3346/jkms.2017.32.5.873.CrossRef

47.

Kawabori M, Weintraub AH, Imai H, Zinkevych L, McAllister P, Steinberg GK, et al. Cell therapy for chronic TBI: interim analysis of the randomized controlled STEMTRA trial. Neurology. 2021;96(8):e1202–14. https://doi.org/10.1212/WNL.0000000000011450.CrossRef

Title: The density of bone marrow mononuclear cells and CD34+ cells in patients with three neurologic conditions
Authors: Kien Trung Nguyen
Nhung Thi My Hoang
Hoang-Phuong Nguyen
Liem Nguyen Thanh
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Central Nervous System Trauma
Icterus
Published in: BMC Neurology / Issue 1/2023
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-023-03071-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The density of bone marrow mononuclear cells and CD34+ cells in patients with three neurologic conditions

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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