Parathyroid Cell Differentiation from Progenitor Cells and Stem Cells: Development, Molecular Mechanism, Function, and Tissue Engineering

Overview

Journal Adv Exp Med Biol

Specialties Biology
General Medicine

Date 2022 Jan 4

PMID 34981451

Citations 2

Authors

Selinay Senkal

Aysegul Dogan

Affiliations

Soon will be listed here.

Abstract

Parathyroid glands are endocrine organs which are located posterior to thyroid glands and control secretion of parathyroid hormone (PTH) in order to regulate blood calcium level. PTH maintains calcium homeostasis by acting on the bone, kidney, and small intestine. PTH deficiency leads to chronic hypocalcemia, organ calcinosis, kidney and heart failure, painful muscle spasms, neuromuscular problems, and memory problems. Since parathyroid cells have inadequate proliferation potential in culture conditions, their utilization as a cellular therapy option is very limited. Although studies conducted so far include parathyroid cell differentiation from various cell types, problems related to successful cellular differentiation and transplantation still remain. Recently, parathyroid tissue engineering has attracted attention as a potential treatment for the parathyroid-related diseases caused by hypoparathyroidism. Although major progression is made in the construction of tissue engineering protocols using parathyroid cells and biomaterials, PTH secretion to mimic its spontaneous harmony in the body is a challenge. This chapter comprehensively defines the derivation of parathyroid cells from various cell sources including pluripotent stem cells, molecular mechanisms, and tissue engineering applications.

Citing Articles

Directed differentiation of human embryonic stem cells into parathyroid cells and establishment of parathyroid organoids.

Wang G, Du Y, Cui X, Xu T, Li H, Dong M Cell Prolif. 2024; 57(8):e13634.

PMID: 38494923 PMC: 11294423. DOI: 10.1111/cpr.13634.

Applications of Metabolomics in Calcium Metabolism Disorders in Humans.

Podgorska B, Wielogorska-Partyka M, Godzien J, Sieminska J, Ciborowski M, Szelachowska M Int J Mol Sci. 2022; 23(18).

PMID: 36142318 PMC: 9499180. DOI: 10.3390/ijms231810407.

References

Bellido T, Saini V, Divieti Pajevic P . Effects of PTH on osteocyte function. Bone. 2012; 54(2):250-7. PMC: 3552098. DOI: 10.1016/j.bone.2012.09.016. View

Bingham E, Cheng S, Woods Ignatoski K, Doherty G . Differentiation of human embryonic stem cells to a parathyroid-like phenotype. Stem Cells Dev. 2008; 18(7):1071-80. DOI: 10.1089/scd.2008.0337. View

Bleul C, Boehm T . BMP signaling is required for normal thymus development. J Immunol. 2005; 175(8):5213-21. DOI: 10.4049/jimmunol.175.8.5213. View

Canaff L, Zhou X, Hendy G . The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3. J Biol Chem. 2008; 283(20):13586-600. DOI: 10.1074/jbc.M708087200. View

Chambers T, Fuller K, McSheehy P, PRINGLE J . The effects of calcium regulating hormones on bone resorption by isolated human osteoclastoma cells. J Pathol. 1985; 145(4):297-305. DOI: 10.1002/path.1711450403. View

Cordier A, Haumont S . Development of thymus, parathyroids, and ultimo-branchial bodies in NMRI and nude mice. Am J Anat. 1980; 157(3):227-63. DOI: 10.1002/aja.1001570303. View

Dang M, Koh A, Jin X, McCauley L, Ma P . Local pulsatile PTH delivery regenerates bone defects via enhanced bone remodeling in a cell-free scaffold. Biomaterials. 2016; 114:1-9. PMC: 5125900. DOI: 10.1016/j.biomaterials.2016.10.049. View

Gardiner J, Jackson A, Gordon J, Lickert H, Manley N, Basson M . Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis. Development. 2012; 139(18):3456-66. PMC: 3424047. DOI: 10.1242/dev.079400. View

Gordon J, Bennett A, Blackburn C, Manley N . Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch. Mech Dev. 2001; 103(1-2):141-3. DOI: 10.1016/s0925-4773(01)00333-1. View

10.

Gordon J, Patel S, Mishina Y, Manley N . Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis. Dev Biol. 2010; 339(1):141-54. PMC: 2823926. DOI: 10.1016/j.ydbio.2009.12.026. View

11.

Greenspan S, Bone H, Ettinger M, Hanley D, Lindsay R, Zanchetta J . Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med. 2007; 146(5):326-39. DOI: 10.7326/0003-4819-146-5-200703060-00005. View

12.

Gunther T, Chen Z, Kim J, Priemel M, Rueger J, Amling M . Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature. 2000; 406(6792):199-203. DOI: 10.1038/35018111. View

13.

Hosoya T, Takizawa K, Nitta K, Hotta Y . glial cells missing: a binary switch between neuronal and glial determination in Drosophila. Cell. 1995; 82(6):1025-36. DOI: 10.1016/0092-8674(95)90281-3. View

14.

Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S . Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest. 1997; 99(12):2961-70. PMC: 508148. DOI: 10.1172/JCI119491. View

15.

Iwaniec U, Moore K, Rivera M, Myers S, Vanegas S, Wronski T . A comparative study of the bone-restorative efficacy of anabolic agents in aged ovariectomized rats. Osteoporos Int. 2006; 18(3):351-62. DOI: 10.1007/s00198-006-0240-9. View

16.

Khryshchanovich V, Ghoussein Y . Allotransplantation of macroencapsulated parathyroid cells as a treatment of severe postsurgical hypoparathyroidism: case report. Ann Saudi Med. 2016; 36(2):143-7. PMC: 6074395. DOI: 10.5144/0256-4947.2016.21.3.1130. View

17.

Kim J, Jones B, Zock C, Chen Z, Wang H, Goodman C . Isolation and characterization of mammalian homologs of the Drosophila gene glial cells missing. Proc Natl Acad Sci U S A. 1998; 95(21):12364-9. PMC: 22837. DOI: 10.1073/pnas.95.21.12364. View

18.

Liu C, Saito F, Liu Z, Lei Y, Uehara S, Love P . Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization. Blood. 2006; 108(8):2531-9. DOI: 10.1182/blood-2006-05-024190. View

19.

Liu Z, Yu S, Manley N . Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia. Dev Biol. 2007; 305(1):333-46. PMC: 1931567. DOI: 10.1016/j.ydbio.2007.02.014. View

20.

Liu Z, Farley A, Chen L, Kirby B, Kovacs C, Blackburn C . Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genet. 2011; 6(12):e1001251. PMC: 3009658. DOI: 10.1371/journal.pgen.1001251. View