Dear stem cell biologists and bioinformaticians: I’ve got a pretty serious question for you. How would you define and quantify the native (endogeneous, in-built) regenerative potential of a tissue/organ or more generally of a specially localized functional cell population in the human body? In the literature the term “regenerative potential” of a tissue is often used concerning the response to damage and repair due to the contribution of the tissue-specific resident stem cell niche or from the circulation, but I haven’t found any strict and quantitative concept and definition yet. If you do please inform me. A working operational definition (update: of a regenerative potential of a tissue/organ) designed to model a conceptual definition could be the basic building block of a whole body regeneration model, which is needed for any attempt to launch systemic regenerative medicine.
So here is my initial offer:
Let us assume that we calculated the following cell numbers of a tissue/organ with some method (stereology, fluorescence activated cell sorter, theorethical calculation based on other measurements and data):
– number of differentiated functional cells
– number of tissue, organ and lineage specific endogenous stem cells
– number of tissue, organ specific progenitor (or transit amplifying cells TACs) cells.
Based on the estimated proportion of stem cell/differentiated cells or TACs/differentiated cells in a defined tissue or organ I’d like to introduce the tissue and organ specific theoretical and practical Regenerative Potential.
I define the Theorethical Regenerative Potential of a tissue or organ as follows: the ratio of quiscent self-renewing stem cells in a stem cell niche/differentiated cells in a tissue or organ. (Or we can use all cells= differentiated+stem+TACs as a denominator.)
Practical Regenerative Potential: the ratio of dividing progenitor cells which give rise to functioning differentiated cells/differentiated cells in a tissue or organ. (Or we can use all cells= differentiated+stem+TACs as a denominator.)
For example: the number of skeletal muscle cells in an adult human being are estimated: 2.50×10(8) or 250 million and the number of satellite cells which are considered as skeletal muscle stem cells is 1.25×10(7) or 12.5 million so the Theorethical Regeneration Potential of human skeletal muscle is 12.5 million/250 million=0.05
Of course it is not advisable to extrapolate from this data to other tissues, because the syncytial and somehow supracellular skeletal muscle is not a typical tissue. And we have to take into consideration the bone-marrow derived or myogenic cell contribution from the circulation.
The other restriction: the significance of this type of Regenerative Potential is dependent of the rate of cellular turnover of organs and tissues, which is rather heterogeneous.