(a) What is stem cell? Discuss the types of stem cells and their application in therapeutic uses in human. 20 (b) Explain the…

(a) Stem cells, their types and therapeutic applications

A stem cell is an unspecialised cell that can renew itself by division and can differentiate into one or more specialised cell types.

Types:

• by potency: totipotent (zygote and early blastomeres, which can form the whole embryo and the placenta); pluripotent (embryonic stem cells from the inner cell mass of the blastocyst, and induced pluripotent cells); multipotent (adult stem cells such as haematopoietic, mesenchymal and neural stem cells, restricted to related cell types); unipotent (for example spermatogonial stem cells)
• by source: embryonic, fetal, adult (bone marrow, adipose tissue, umbilical cord blood) and induced pluripotent stem cells (iPSCs), made by reprogramming somatic cells with Oct4, Sox2, Klf4 and c-Myc (Takahashi and Yamanaka, 2006–07; Nobel Prize 2012)

Therapeutic uses in humans:

• haematopoietic stem cell transplantation (bone marrow, peripheral blood or cord blood) is the established therapy for leukaemias, lymphomas, aplastic anaemia, thalassaemia and sickle-cell disease; gene-edited autologous blood stem cells (exa-cel) were approved in 2023–24 for sickle-cell disease and β-thalassaemia
• cultured epidermal stem cells cover severe burns, and cultured limbal stem cells repair the cornea damaged by burns
• mesenchymal stem cells are used for graft-versus-host disease and are being tested for bone and cartilage repair
• ESC- or iPSC-derived cells are in trials for Parkinson's disease, macular degeneration, type 1 diabetes, heart disease and spinal cord injury
• stem cells also serve for disease modelling, drug testing and tissue engineering

Limits: tumour (teratoma) risk, immune rejection (reduced with the patient's own iPSCs), ethical objections to destroying embryos, and unproven commercial therapies. In India only haematopoietic transplantation is a permitted treatment; other uses need approved clinical trials (National Guidelines for Stem Cell Research, 2017).

(b) Spermatogenesis in mammals

Spermatogenesis is the formation of haploid spermatozoa from diploid germ cells in the seminiferous tubules of the testis, beginning at puberty. The labelled diagram should show a section of a seminiferous tubule from the basement membrane to the lumen:

• spermatogonia (2n) on the basement membrane, with Sertoli cells and the blood–testis barrier
• primary spermatocytes (2n) in meiosis I, then secondary spermatocytes (n) in meiosis II
• spermatids (n) and spermatozoa embedded in Sertoli cells, with the spermatozoa released into the lumen
• Leydig cells between the tubules, and a flow chart with human chromosome numbers (46, 46, 23, 23)

Stages:

1. Multiplication: spermatogonia divide by mitosis; some remain as stem cells and others grow into primary spermatocytes.
2. Growth: the primary spermatocyte (2n) enlarges and replicates its DNA.
3. Maturation: meiosis I gives two secondary spermatocytes (n) and meiosis II gives four spermatids (n), so each primary spermatocyte yields four sperm.
4. Spermiogenesis: each spermatid becomes a sperm without dividing; the nucleus condenses, the Golgi forms the acrosome, the centriole forms the tail axoneme, mitochondria gather in the middle piece, and spare cytoplasm is shed as a residual body that Sertoli cells engulf.
5. Spermiation: sperm are released into the lumen and pass to the epididymis. The cycle takes about 74 days in humans.

Control: GnRH from the hypothalamus makes the pituitary release LH, which acts on Leydig cells to make testosterone, and FSH, which acts on Sertoli cells (androgen-binding protein, inhibin). Sertoli cells nourish and support the germ cells.

(c) Hormonal regulation of metamorphosis in amphibians

Metamorphosis, the change of a gill-breathing tadpole into a lung-breathing tailless frog, is controlled mainly by thyroid hormones (T₄ and T₃) through the hypothalamus–pituitary–thyroid axis, modified by corticosteroids and prolactin.

Hormonal chain:

1. The hypothalamus releases corticotropin-releasing hormone (CRH), the main TSH-releasing factor in tadpoles.
2. The pituitary secretes TSH, which makes the thyroid release T₄ (the chief product) and some T₃.
3. Tissues convert T₄ to the more active T₃ by deiodinases; T₃ binds nuclear receptors and switches on tissue-specific genes. T₃ also feeds back negatively on TSH.

Stages:

• premetamorphosis: thyroid hormone is low; the tadpole grows and hind-limb buds form
• prometamorphosis: thyroid hormone rises; hind limbs grow and toes differentiate
• metamorphic climax: hormone peaks; forelimbs emerge, the tail is resorbed by apoptosis, gills and larval mouth parts are lost, the gut shortens, the liver changes from ammonia to urea formation and the haemoglobin type changes

Other hormones: corticosteroids rise with thyroid hormone, increase tissue sensitivity to T₃ and speed the climax. Prolactin, regarded as a juvenilising hormone, opposes thyroid hormone action, although its exact role is debated.

Evidence: feeding thyroid tissue (Gudernatsch, 1912) causes early metamorphosis; thyroidectomy (Allen, 1916) or hypophysectomy gives giant tadpoles that never metamorphose; and the neotenic axolotl metamorphoses when given thyroxine.